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palosuran (MedChemExpress)

Name: palosuran
Brand: MedChemExpress
Rating: 92 (3 reviews)

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MedChemExpress palosuran

a – e Antagonistic effect of <t>palosuran,</t> GSK1562590 and ligand bias of urantide on the activation of G proteins and β-arrestins on UII-activated UT signaling pathways (3 independent experiments for each in triplicate each). a Using BRET biosensors, UII activation of G i coupled family members Gαi1, Gαi2, Gαi3, and Gαz was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists. b The activation of the G q pathway was accessed using both a BRET biosensor and by determining the production levels of the second messenger IP 1 in the presence of 10 µM of the indicated biased ligand/antagonists. c Ca 2+ mobilization induced by graded concentrations (10 −11 to 10 −6 M) of UII on hUT-transfected HEK-293 cells pretreated with buffer or biased ligand/antagonists. d Using BRET biosensors, UII activation of G o coupled family members GoA and GoB was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists. e Using BRET biosensors, the UII-induced recruitment of β-arrestin 1 and β-arrestin 2 was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists ( a – e , n = 3; values are expressed as the mean ± SEM). f Timeline of intracisternal injection of palosuran, GSK1562590 or urantide during SAH induction prior to CVS analysis and behavioral testing. g Graphs (right panel) representing changes in lumen area/wall thickness on MCA ( n = 6/condition). Values are expressed as the mean ± SEM. *** P < 0.001 for comparisons with aCSF + sham condition. $$$ P < 0.001 for comparisons with aCSF + SAH condition (two-sided one-way analysis of variance (ANOVA), Bonferroni’s correction). Exploration in OFT (10 min) and sensorimotor functions in BWT ( n = 6–10/condition). Values are expressed as the mean ± SEM * P < 0.05; ** P < 0.01; *** P < 0.001 for comparisons with aCSF + sham condition. $ P < 0.05; $$ P < 0.01; $$$ P < 0.001 for comparisons with aCSF + SAH condition (two-sided one-way analysis of variance (ANOVA), Bonferroni’s correction). Source data are provided as a Source Data file. f created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license ( https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en ).

Palosuran, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 92/100, based on 3 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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palosuran - by Bioz Stars, 2026-03

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1) Product Images from "The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice"

Article Title: The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice

Journal: Nature Communications

doi: 10.1038/s41467-024-52654-2

a – e Antagonistic effect of palosuran, GSK1562590 and ligand bias of urantide on the activation of G proteins and β-arrestins on UII-activated UT signaling pathways (3 independent experiments for each in triplicate each). a Using BRET biosensors, UII activation of G i coupled family members Gαi1, Gαi2, Gαi3, and Gαz was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists. b The activation of the G q pathway was accessed using both a BRET biosensor and by determining the production levels of the second messenger IP 1 in the presence of 10 µM of the indicated biased ligand/antagonists. c Ca 2+ mobilization induced by graded concentrations (10 −11 to 10 −6 M) of UII on hUT-transfected HEK-293 cells pretreated with buffer or biased ligand/antagonists. d Using BRET biosensors, UII activation of G o coupled family members GoA and GoB was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists. e Using BRET biosensors, the UII-induced recruitment of β-arrestin 1 and β-arrestin 2 was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists ( a – e , n = 3; values are expressed as the mean ± SEM). f Timeline of intracisternal injection of palosuran, GSK1562590 or urantide during SAH induction prior to CVS analysis and behavioral testing. g Graphs (right panel) representing changes in lumen area/wall thickness on MCA ( n = 6/condition). Values are expressed as the mean ± SEM. *** P < 0.001 for comparisons with aCSF + sham condition. $$$ P < 0.001 for comparisons with aCSF + SAH condition (two-sided one-way analysis of variance (ANOVA), Bonferroni’s correction). Exploration in OFT (10 min) and sensorimotor functions in BWT ( n = 6–10/condition). Values are expressed as the mean ± SEM * P < 0.05; ** P < 0.01; *** P < 0.001 for comparisons with aCSF + sham condition. $ P < 0.05; $$ P < 0.01; $$$ P < 0.001 for comparisons with aCSF + SAH condition (two-sided one-way analysis of variance (ANOVA), Bonferroni’s correction). Source data are provided as a Source Data file. f created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license ( https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en ).

Figure Legend Snippet: a – e Antagonistic effect of palosuran, GSK1562590 and ligand bias of urantide on the activation of G proteins and β-arrestins on UII-activated UT signaling pathways (3 independent experiments for each in triplicate each). a Using BRET biosensors, UII activation of G i coupled family members Gαi1, Gαi2, Gαi3, and Gαz was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists. b The activation of the G q pathway was accessed using both a BRET biosensor and by determining the production levels of the second messenger IP 1 in the presence of 10 µM of the indicated biased ligand/antagonists. c Ca 2+ mobilization induced by graded concentrations (10 −11 to 10 −6 M) of UII on hUT-transfected HEK-293 cells pretreated with buffer or biased ligand/antagonists. d Using BRET biosensors, UII activation of G o coupled family members GoA and GoB was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists. e Using BRET biosensors, the UII-induced recruitment of β-arrestin 1 and β-arrestin 2 was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists ( a – e , n = 3; values are expressed as the mean ± SEM). f Timeline of intracisternal injection of palosuran, GSK1562590 or urantide during SAH induction prior to CVS analysis and behavioral testing. g Graphs (right panel) representing changes in lumen area/wall thickness on MCA ( n = 6/condition). Values are expressed as the mean ± SEM. *** P < 0.001 for comparisons with aCSF + sham condition. $$$ P < 0.001 for comparisons with aCSF + SAH condition (two-sided one-way analysis of variance (ANOVA), Bonferroni’s correction). Exploration in OFT (10 min) and sensorimotor functions in BWT ( n = 6–10/condition). Values are expressed as the mean ± SEM * P < 0.05; ** P < 0.01; *** P < 0.001 for comparisons with aCSF + sham condition. $ P < 0.05; $$ P < 0.01; $$$ P < 0.001 for comparisons with aCSF + SAH condition (two-sided one-way analysis of variance (ANOVA), Bonferroni’s correction). Source data are provided as a Source Data file. f created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license ( https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en ).

Techniques Used: Activation Assay, Expressing, Transfection, Injection

Image Search Results

Journal: Nature Communications

Article Title: The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice

doi: 10.1038/s41467-024-52654-2

Figure Lengend Snippet: a – e Antagonistic effect of palosuran, GSK1562590 and ligand bias of urantide on the activation of G proteins and β-arrestins on UII-activated UT signaling pathways (3 independent experiments for each in triplicate each). a Using BRET biosensors, UII activation of G i coupled family members Gαi1, Gαi2, Gαi3, and Gαz was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists. b The activation of the G q pathway was accessed using both a BRET biosensor and by determining the production levels of the second messenger IP 1 in the presence of 10 µM of the indicated biased ligand/antagonists. c Ca 2+ mobilization induced by graded concentrations (10 −11 to 10 −6 M) of UII on hUT-transfected HEK-293 cells pretreated with buffer or biased ligand/antagonists. d Using BRET biosensors, UII activation of G o coupled family members GoA and GoB was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists. e Using BRET biosensors, the UII-induced recruitment of β-arrestin 1 and β-arrestin 2 was assessed in HEK293 cells transiently expressing hUT in the presence of 10 µM of the indicated biased ligand/antagonists ( a – e , n = 3; values are expressed as the mean ± SEM). f Timeline of intracisternal injection of palosuran, GSK1562590 or urantide during SAH induction prior to CVS analysis and behavioral testing. g Graphs (right panel) representing changes in lumen area/wall thickness on MCA ( n = 6/condition). Values are expressed as the mean ± SEM. *** P < 0.001 for comparisons with aCSF + sham condition. $$$ P < 0.001 for comparisons with aCSF + SAH condition (two-sided one-way analysis of variance (ANOVA), Bonferroni’s correction). Exploration in OFT (10 min) and sensorimotor functions in BWT ( n = 6–10/condition). Values are expressed as the mean ± SEM * P < 0.05; ** P < 0.01; *** P < 0.001 for comparisons with aCSF + sham condition. $ P < 0.05; $$ P < 0.01; $$$ P < 0.001 for comparisons with aCSF + SAH condition (two-sided one-way analysis of variance (ANOVA), Bonferroni’s correction). Source data are provided as a Source Data file. f created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license ( https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en ).

Article Snippet: Finally, urantide (synthetized by Dr. Marc André Bonin, peptide synthesis platform, Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Quebec, Canada), GSK1562590 (Tocris, #5110) and palosuran (MedChemExpress, #HY-10655) were diluted in blood and intracisternally injected during SAH induction (10 -5 M, 60 µl at D-1, 30 µl at D0), and were also used for in vitro pharmacological experiments.

Techniques: Activation Assay, Expressing, Transfection, Injection

Blood glucose levels and changes in body weight of experimental rat groups.

Journal: Asian Journal of Urology

Article Title: The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats

doi: 10.1016/j.ajur.2024.02.010

Figure Lengend Snippet: Blood glucose levels and changes in body weight of experimental rat groups.

Article Snippet: After confirmation of DM, palosuran-treated diabetic group received daily oral doses of 300 mg/kg per day palosuran (ACT-058362, Actelion Pharmaceuticals, Allschwil, Switzerland) administered via a gastric tube for 6 weeks.

Techniques: Control

Contractile responses of rat corpora cavernosa in the isolated organ baths. (A) KCl (120 mmol/L)-induced contractile responses ( n =9–15); (B) Response curves to cumulative concentrations of PE (doses of the PE have been presented as the negative logarithm [−log 10 ] of its concentrations applied; n =9–15); (C) Additional contractile responses of PE-precontracted strips to 100 μmol/L l -NAME ( n =7–12). DM, diabetes mellitus; DM+palosuran, DM treated with palosuran; l -NAME, NG-nitro-L-arginine methyl ester; PE, phenylephrine. ∗ p< 0.05 and ∗∗ p< 0.01 vs. the control group.

Journal: Asian Journal of Urology

Article Title: The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats

doi: 10.1016/j.ajur.2024.02.010

Figure Lengend Snippet: Contractile responses of rat corpora cavernosa in the isolated organ baths. (A) KCl (120 mmol/L)-induced contractile responses ( n =9–15); (B) Response curves to cumulative concentrations of PE (doses of the PE have been presented as the negative logarithm [−log 10 ] of its concentrations applied; n =9–15); (C) Additional contractile responses of PE-precontracted strips to 100 μmol/L l -NAME ( n =7–12). DM, diabetes mellitus; DM+palosuran, DM treated with palosuran; l -NAME, NG-nitro-L-arginine methyl ester; PE, phenylephrine. ∗ p< 0.05 and ∗∗ p< 0.01 vs. the control group.

Techniques: Isolation, Control

Relaxation of PE-precontracted rat cavernosal strips. (A) Frequency response curves with EFS, in the presence of atropine and guanethidine ( n =8–15); (B) Response curves to cumulative concentrations of SNP ( n =11–16); (C) The pD 2 values of SNP ( n =9−11); (D) Response curves to cumulative concentrations of Y-27632 ( n =10–15); (E) The pD 2 values of Y-27632 ( n =10–15); (F) Response curves to cumulative concentrations of palosuran administered in vitro directly ( n =5–6). Relaxation responses are presented as the percentage of the PE-precontraction in the A, B , D, and F. In the cumulative dose–response curves (B, D, and F), doses of agents have been presented as the negative logarithm (−log 10 ) of their concentrations applied. PE, phenylephrine; EFS, electrical field stimulation; SNP, sodium nitroprusside; DM, diabetes mellitus; DM+palosuran, DM treated with palosuran. ∗ p< 0.05, ∗∗ p< 0.01, ∗∗∗ p <0.001 vs. the control group; # p< 0.05 and ## p< 0.01 vs. the untreated diabetic group.

Journal: Asian Journal of Urology

Article Title: The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats

doi: 10.1016/j.ajur.2024.02.010

Figure Lengend Snippet: Relaxation of PE-precontracted rat cavernosal strips. (A) Frequency response curves with EFS, in the presence of atropine and guanethidine ( n =8–15); (B) Response curves to cumulative concentrations of SNP ( n =11–16); (C) The pD 2 values of SNP ( n =9−11); (D) Response curves to cumulative concentrations of Y-27632 ( n =10–15); (E) The pD 2 values of Y-27632 ( n =10–15); (F) Response curves to cumulative concentrations of palosuran administered in vitro directly ( n =5–6). Relaxation responses are presented as the percentage of the PE-precontraction in the A, B , D, and F. In the cumulative dose–response curves (B, D, and F), doses of agents have been presented as the negative logarithm (−log 10 ) of their concentrations applied. PE, phenylephrine; EFS, electrical field stimulation; SNP, sodium nitroprusside; DM, diabetes mellitus; DM+palosuran, DM treated with palosuran. ∗ p< 0.05, ∗∗ p< 0.01, ∗∗∗ p <0.001 vs. the control group; # p< 0.05 and ## p< 0.01 vs. the untreated diabetic group.

Techniques: In Vitro, Control

Representative band images and the expression levels obtained by Western blotting of proteins in rat corpora cavernosa. (A) nNOS; (B) RhoA; (C) iNOS; (D) p65 (a subgroup of NF-κb). n =4–6 for each parameter. DM, diabetes mellitus; DM+palosuran, DM treated with palosuran; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B; nNOS, neuronal nitric oxide synthase. ∗ p <0.05 and ∗∗ p <0.01 vs. the control group; # p< 0.05 and ## p< 0.01 vs. the untreated DM group. The results were normalized to β-actin which was considered as 1.00.

Journal: Asian Journal of Urology

Article Title: The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats

doi: 10.1016/j.ajur.2024.02.010

Figure Lengend Snippet: Representative band images and the expression levels obtained by Western blotting of proteins in rat corpora cavernosa. (A) nNOS; (B) RhoA; (C) iNOS; (D) p65 (a subgroup of NF-κb). n =4–6 for each parameter. DM, diabetes mellitus; DM+palosuran, DM treated with palosuran; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor kappa B; nNOS, neuronal nitric oxide synthase. ∗ p <0.05 and ∗∗ p <0.01 vs. the control group; # p< 0.05 and ## p< 0.01 vs. the untreated DM group. The results were normalized to β-actin which was considered as 1.00.

Techniques: Expressing, Western Blot, Control

Representative images and expression levels in the rat corpora cavernosa obtained by immunohistochemistry. (A) eNOS; (B) U-II. DM, diabetes mellitus; DM+palosuran, DM treated with palosuran; eNOS, endothelial nitric oxide synthase; U-II, urotensin-II. Red and black arrows indicate eNOS and U-II proteins, respectively; stars indicate sinusoidal areas. Scale bar: 100 μm. n =4–6. ∗ p< 0.05 vs. the control group; # p< 0.05 vs. the untreated diabetic group. To provide a more distinct representation, the background of the images has been made transparent and their clarity has been increased.

Journal: Asian Journal of Urology

Article Title: The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats

doi: 10.1016/j.ajur.2024.02.010

Figure Lengend Snippet: Representative images and expression levels in the rat corpora cavernosa obtained by immunohistochemistry. (A) eNOS; (B) U-II. DM, diabetes mellitus; DM+palosuran, DM treated with palosuran; eNOS, endothelial nitric oxide synthase; U-II, urotensin-II. Red and black arrows indicate eNOS and U-II proteins, respectively; stars indicate sinusoidal areas. Scale bar: 100 μm. n =4–6. ∗ p< 0.05 vs. the control group; # p< 0.05 vs. the untreated diabetic group. To provide a more distinct representation, the background of the images has been made transparent and their clarity has been increased.

Techniques: Expressing, Immunohistochemistry, Control

Names, sequences, and characteristics of the different urotensinergic peptide and non-peptide ligands used in the study.

Journal: Frontiers in Cell and Developmental Biology

Article Title: Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma

doi: 10.3389/fcell.2021.652544

Figure Lengend Snippet: Names, sequences, and characteristics of the different urotensinergic peptide and non-peptide ligands used in the study.

Article Snippet: Endothelial cells (5 × 10 4 cells/cm 2 ) were seeded in basal medium and incubated for 24 h in the absence or the presence of UT agonists (Phoenix Pharmaceuticals, Inc) (UII, mUII, URP, UII 4 – 11 , ) at 10 –12 to 10 –7 M, the UT antagonist/biased ligand urantide (Peptides International, Louisville, KY, United States, ), or the UT antagonist palosuran (Actelion Pharmaceuticals, Allschwil, Switzerland, ) from 10 –10 to 10 –7 M. Phase contrast image analysis was carried out using ImageJ software.

Techniques:

In vitro effect of urotensinergic ligands on human glioma and endothelial cell migration and tubulogenesis. (A) Microphotographs of UT and UII staining on the GBM cell line U87 and EC hCMEC/D3 from human origins. Scale bar, 20 μm. (B) Representative fields ( Top panel ) of migrating U87 and hCMEC/D3 cells quantified from the Boyden chamber assay and quantification of U87 ( Left ) and hCMEC/D3 ( Right ) cell number in the absence or the presence of FBS 10% or UII (10 –12 , 10 –11 , 10 –10 , 10 –9 , or 10 –8 M). (C) Microphotographs of the tubulogenesis assay illustrating in vitro properties of UT agonists (UII, URP, and UII 4 – 11 ), biased ligand (urantide), or antagonist (palosuran) on angiogenic features of hCMEC/D3 and HUV-EC-C cells. Scale bars, 400 μm. (D) Data are presented as the% of control ± SEM from six independent experiments, and branch length, major junctions, and segment number were quantified and compared to control conditions. Statistical significance of treatments vs. control condition was assessed with one-way ANOVA with Dunnett post hoc test. ns, non-significant; * P < 0.05; ** P < 0.01; *** P < 0.001. Statistical significance of co-treatments (UII + urantide; UII + palosuran) vs. UII alone was conducted with Student t -test. ## P < 0.01; ### P < 0.001.

Journal: Frontiers in Cell and Developmental Biology

Article Title: Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma

doi: 10.3389/fcell.2021.652544

Figure Lengend Snippet: In vitro effect of urotensinergic ligands on human glioma and endothelial cell migration and tubulogenesis. (A) Microphotographs of UT and UII staining on the GBM cell line U87 and EC hCMEC/D3 from human origins. Scale bar, 20 μm. (B) Representative fields ( Top panel ) of migrating U87 and hCMEC/D3 cells quantified from the Boyden chamber assay and quantification of U87 ( Left ) and hCMEC/D3 ( Right ) cell number in the absence or the presence of FBS 10% or UII (10 –12 , 10 –11 , 10 –10 , 10 –9 , or 10 –8 M). (C) Microphotographs of the tubulogenesis assay illustrating in vitro properties of UT agonists (UII, URP, and UII 4 – 11 ), biased ligand (urantide), or antagonist (palosuran) on angiogenic features of hCMEC/D3 and HUV-EC-C cells. Scale bars, 400 μm. (D) Data are presented as the% of control ± SEM from six independent experiments, and branch length, major junctions, and segment number were quantified and compared to control conditions. Statistical significance of treatments vs. control condition was assessed with one-way ANOVA with Dunnett post hoc test. ns, non-significant; * P < 0.05; ** P < 0.01; *** P < 0.001. Statistical significance of co-treatments (UII + urantide; UII + palosuran) vs. UII alone was conducted with Student t -test. ## P < 0.01; ### P < 0.001.

Techniques: In Vitro, Migration, Staining, Boyden Chamber Assay

In vivo chemoattractant effects of the urotensinergic ligands toward pro-angiogenic cells in Matrigel plugs. (A,B) Macrophotographs of resected Matrigel plugs (200 μl) containing vehicle (PBS), EGF (500 ng), EG-VEGF (500 ng) (A) or UII, mUII, URP, UII 4 – 11 (50 ng, each), urantide (50 ng), or palosuran (50 ng) (B) 3 weeks after implantation in C57B/l6 mice. Matrigel invasion was detected by immunohistochemical analysis of macrophages (F4/80, red), EC matrix collagen-IV (COLL-IV, red), and smooth muscle cells (α-SMA, green). Scale bars, 40 μm. Quantification of macrophage number or smooth muscle cell and EC structure areas. Data are presented as percentage of control ± SEM. * P < 0.05; ** P < 0.01; *** P < 0.001 from at least four independent experiments. Statistical significance is given by one-way ANOVA with Dunnett post hoc test vs. control.

Journal: Frontiers in Cell and Developmental Biology

Article Title: Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma

doi: 10.3389/fcell.2021.652544

Figure Lengend Snippet: In vivo chemoattractant effects of the urotensinergic ligands toward pro-angiogenic cells in Matrigel plugs. (A,B) Macrophotographs of resected Matrigel plugs (200 μl) containing vehicle (PBS), EGF (500 ng), EG-VEGF (500 ng) (A) or UII, mUII, URP, UII 4 – 11 (50 ng, each), urantide (50 ng), or palosuran (50 ng) (B) 3 weeks after implantation in C57B/l6 mice. Matrigel invasion was detected by immunohistochemical analysis of macrophages (F4/80, red), EC matrix collagen-IV (COLL-IV, red), and smooth muscle cells (α-SMA, green). Scale bars, 40 μm. Quantification of macrophage number or smooth muscle cell and EC structure areas. Data are presented as percentage of control ± SEM. * P < 0.05; ** P < 0.01; *** P < 0.001 from at least four independent experiments. Statistical significance is given by one-way ANOVA with Dunnett post hoc test vs. control.

Techniques: In Vivo, Immunohistochemical staining

Effects of the urotensinergic system on glioma development in vivo. (A) Tumor growth ( left ) and survival ( right ) of Swiss Nude mice transplanted with U87 cells. When tumor reached 100 mm 3 , intratumoral injections of vehicle (saline) or UII (0.1 μg) were performed daily and tumor growth or median survival of treated mice was measured. ** P < 0.01; *** P < 0.001. Median survival: vehicle ( n = 7), 33 days; UII ( n = 7), 22 days ( P = 0.0126). (B) Microphotographs of UT (green) and UII (red) expression in vehicle (PBS)- and UII-treated U87 xenografts. UII and UT were expressed in tumor parenchyma, in perinecrotic (N) areas and in vascular structures. (C) Tumor growth ( Left ) and mice survival ( Right ) during treatments with vehicle, URP, or UII 4 – 11 (0.1 μg, each) of xenografted U87. Median survival: vehicle ( n = 4), 22 days; URP ( n = 4), 28 days ( P = 0.5875); UII 4 – 11 ( n = 4), 26 days ( P = 0.8931). (D) Top panel, typical gallery of representative example of U87 xenografts treated with vehicle, UII (0.1 μg), palosuran (1 μg), UII + palosuran (0.1/1 μg), urantide (1 μg), and UII + urantide (0.1/1 μg). Middle panel, tumor growth during the different treatments. * P < 0.05; ** P < 0.01; *** P < 0.001. Bottom panel, mice survival during the different treatments. Median survival: vehicle ( n = 10), 23 days; UII ( n = 10), 16 days ( P = 0.0005); palosuran ( n = 10), 23 days ( P = 0.2922), UII + palosuran ( n = 9), 23 days ( P = 0.86), urantide ( n = 10), 43 days ( P = 0.0067), UII + urantide ( n = 10), 27 days ( P = 0.0645). (E) Immunolabeling of UT (green) and UII (red), and tumor distribution in vehicle, UII, urantide, and UII + urantide-treated U87 xenografts. Data presented as mean ± SEM. Animal survival was analyzed with Kaplan–Meier method, using the log-rank test for comparison. Statistical significance for tumor growth in (A,C,D) was given by using two-way ANOVA with Bonferroni post hoc test comparison with vehicle. Cell nuclei stained with DAPI (blue). Scale bars: 20 μm.

Journal: Frontiers in Cell and Developmental Biology

Article Title: Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma

doi: 10.3389/fcell.2021.652544

Figure Lengend Snippet: Effects of the urotensinergic system on glioma development in vivo. (A) Tumor growth ( left ) and survival ( right ) of Swiss Nude mice transplanted with U87 cells. When tumor reached 100 mm 3 , intratumoral injections of vehicle (saline) or UII (0.1 μg) were performed daily and tumor growth or median survival of treated mice was measured. ** P < 0.01; *** P < 0.001. Median survival: vehicle ( n = 7), 33 days; UII ( n = 7), 22 days ( P = 0.0126). (B) Microphotographs of UT (green) and UII (red) expression in vehicle (PBS)- and UII-treated U87 xenografts. UII and UT were expressed in tumor parenchyma, in perinecrotic (N) areas and in vascular structures. (C) Tumor growth ( Left ) and mice survival ( Right ) during treatments with vehicle, URP, or UII 4 – 11 (0.1 μg, each) of xenografted U87. Median survival: vehicle ( n = 4), 22 days; URP ( n = 4), 28 days ( P = 0.5875); UII 4 – 11 ( n = 4), 26 days ( P = 0.8931). (D) Top panel, typical gallery of representative example of U87 xenografts treated with vehicle, UII (0.1 μg), palosuran (1 μg), UII + palosuran (0.1/1 μg), urantide (1 μg), and UII + urantide (0.1/1 μg). Middle panel, tumor growth during the different treatments. * P < 0.05; ** P < 0.01; *** P < 0.001. Bottom panel, mice survival during the different treatments. Median survival: vehicle ( n = 10), 23 days; UII ( n = 10), 16 days ( P = 0.0005); palosuran ( n = 10), 23 days ( P = 0.2922), UII + palosuran ( n = 9), 23 days ( P = 0.86), urantide ( n = 10), 43 days ( P = 0.0067), UII + urantide ( n = 10), 27 days ( P = 0.0645). (E) Immunolabeling of UT (green) and UII (red), and tumor distribution in vehicle, UII, urantide, and UII + urantide-treated U87 xenografts. Data presented as mean ± SEM. Animal survival was analyzed with Kaplan–Meier method, using the log-rank test for comparison. Statistical significance for tumor growth in (A,C,D) was given by using two-way ANOVA with Bonferroni post hoc test comparison with vehicle. Cell nuclei stained with DAPI (blue). Scale bars: 20 μm.

Techniques: In Vivo, Expressing, Immunolabeling, Staining

Effects of the urotensinergic system on cell proliferation, hypoxia, and necrosis in U87 GBM. (A) Representative microscopic fields ( Top panel ) of U87 xenografts immunostained with an antibody directed against the proliferation marker Ki67 (red). Bottom left, quantification of the number of proliferative cells (Ki67 + ) after 15 days of daily intratumoral injections of the UT ligands; bottom right, linear regression of tumor volume vs. proliferation index. Statistical significance of vehicle versus UII, palosuran, urantide, or co-treatments at day 15. ** P < 0.01; *** P < 0.001. Statistical significance of UII versus co-treatments at day 15. ###P < 0.001. A significant positive correlation was given by the Pearson coefficient correlation r = 0.6579 ( P < 0.0001). Scale bars: 40 μm. (B) Top, microscopic fields of U87 xenografts of tumoral hypoxia revealed by pimonidazole labeling (green) after 15 days of daily intratumoral injections of vehicle, UII (0.1 μg), or urantide (1 μg). Bottom, quantification of pimonidazole stained area ( Left ) and intensity ( Right ). Scale bars: 40 μm. n = 4 in each treatment groups. *** P < 0.001. (C) Top, H&E necrotic area coloration after 15 days of daily intratumoral injections of vehicle, UII (0.1 μg), or urantide (1 μg). Bottom, quantification of the necrotic area after 15 days ( left ) or after tumors reached 1000 mm 3 ( Right ). Scale bars: 2 mm. n = 6 in each treatment groups. ** P < 0.01; *** P < 0.001.

Journal: Frontiers in Cell and Developmental Biology

Article Title: Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma

doi: 10.3389/fcell.2021.652544

Figure Lengend Snippet: Effects of the urotensinergic system on cell proliferation, hypoxia, and necrosis in U87 GBM. (A) Representative microscopic fields ( Top panel ) of U87 xenografts immunostained with an antibody directed against the proliferation marker Ki67 (red). Bottom left, quantification of the number of proliferative cells (Ki67 + ) after 15 days of daily intratumoral injections of the UT ligands; bottom right, linear regression of tumor volume vs. proliferation index. Statistical significance of vehicle versus UII, palosuran, urantide, or co-treatments at day 15. ** P < 0.01; *** P < 0.001. Statistical significance of UII versus co-treatments at day 15. ###P < 0.001. A significant positive correlation was given by the Pearson coefficient correlation r = 0.6579 ( P < 0.0001). Scale bars: 40 μm. (B) Top, microscopic fields of U87 xenografts of tumoral hypoxia revealed by pimonidazole labeling (green) after 15 days of daily intratumoral injections of vehicle, UII (0.1 μg), or urantide (1 μg). Bottom, quantification of pimonidazole stained area ( Left ) and intensity ( Right ). Scale bars: 40 μm. n = 4 in each treatment groups. *** P < 0.001. (C) Top, H&E necrotic area coloration after 15 days of daily intratumoral injections of vehicle, UII (0.1 μg), or urantide (1 μg). Bottom, quantification of the necrotic area after 15 days ( left ) or after tumors reached 1000 mm 3 ( Right ). Scale bars: 2 mm. n = 6 in each treatment groups. ** P < 0.01; *** P < 0.001.

Techniques: Marker, Labeling, Staining

Effects of the urotensinergic system on angiogenesis in U87 GBM. (A) UII (Top) and UT (Bottom) (red, each) immunostainings co-localized with VSMC and EC detected with anti-αSMA and anti-CD31 (green), respectively, in U87 xenografts. (B) COLL-IV (red) labeling in U87 tumors after 15 days of different treatments ( left panel ) or after tumors reach 1000 mm 3 ( right panel ). Quantification of intratumoral angiogenesis (vascular area) after 15 days of treatments or after tumors reach 1000 mm 3 (vascular area, number of branches and vessel diameter) as percentage of control ± SEM. ** P < 0.01; *** P < 0.001 vehicle vs. treatments; ## P < 0.05; ### P < 0.001; UII versus UII + palosuran or UII + urantide, from at least four different tumors in each group. Statistical significance was given by one-way ANOVA followed by Dunnett post hoc test. UC , uncountable.

Journal: Frontiers in Cell and Developmental Biology

Article Title: Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma

doi: 10.3389/fcell.2021.652544

Figure Lengend Snippet: Effects of the urotensinergic system on angiogenesis in U87 GBM. (A) UII (Top) and UT (Bottom) (red, each) immunostainings co-localized with VSMC and EC detected with anti-αSMA and anti-CD31 (green), respectively, in U87 xenografts. (B) COLL-IV (red) labeling in U87 tumors after 15 days of different treatments ( left panel ) or after tumors reach 1000 mm 3 ( right panel ). Quantification of intratumoral angiogenesis (vascular area) after 15 days of treatments or after tumors reach 1000 mm 3 (vascular area, number of branches and vessel diameter) as percentage of control ± SEM. ** P < 0.01; *** P < 0.001 vehicle vs. treatments; ## P < 0.05; ### P < 0.001; UII versus UII + palosuran or UII + urantide, from at least four different tumors in each group. Statistical significance was given by one-way ANOVA followed by Dunnett post hoc test. UC , uncountable.

Techniques: Labeling

Schematic model illustrating the pleiotrope functions of the urotensinergic system during GBM malignancy. The UT receptor when expressed at both the tumoral and vascular compartments, and activated by UII through endogenous release by tumor cells, relayed accelerated tumor growth and proliferation, hypoxia, and necrosis, leading to exacerbation of the abnormal and tortuous vascularization. These processes are accompanied by metalloprotease (MMPs) release such as MMP-9 by the endothelial compartment likely degrading extracellular matrix, and by increased expression of αv(β3) integrins at least in part by GBM cells. The hypothesis of a contributing mechanism of a UII-induced macrophage tumor invasion can also be proposed, as potential cell partners in necrosis and angiogenesis. UT receptor antagonist palosuran or the biased ligand urantide would constitute a new original strategy to prevent glioma malignancy. Here, the biased ligand urantide exhibits a better multicellular anti-UT activity than palosuran both repressing angiogenesis and tumor growth, suggesting a new avenue for GBM treatment targeting the urotensinergic system.

Journal: Frontiers in Cell and Developmental Biology

Article Title: Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma

doi: 10.3389/fcell.2021.652544

Figure Lengend Snippet: Schematic model illustrating the pleiotrope functions of the urotensinergic system during GBM malignancy. The UT receptor when expressed at both the tumoral and vascular compartments, and activated by UII through endogenous release by tumor cells, relayed accelerated tumor growth and proliferation, hypoxia, and necrosis, leading to exacerbation of the abnormal and tortuous vascularization. These processes are accompanied by metalloprotease (MMPs) release such as MMP-9 by the endothelial compartment likely degrading extracellular matrix, and by increased expression of αv(β3) integrins at least in part by GBM cells. The hypothesis of a contributing mechanism of a UII-induced macrophage tumor invasion can also be proposed, as potential cell partners in necrosis and angiogenesis. UT receptor antagonist palosuran or the biased ligand urantide would constitute a new original strategy to prevent glioma malignancy. Here, the biased ligand urantide exhibits a better multicellular anti-UT activity than palosuran both repressing angiogenesis and tumor growth, suggesting a new avenue for GBM treatment targeting the urotensinergic system.

Techniques: Expressing, Activity Assay

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1) Product Images from "The urotensin II receptor triggers an early meningeal response and a delayed macrophage-dependent vasospasm after subarachnoid hemorrhage in male mice"

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