Journal: Journal of Cell Science

Article Title: Epithelial plasticity in COPD results in cellular unjamming due to an increase in polymerized actin

doi: 10.1242/jcs.258513

Figure Lengend Snippet: Inhibitors of actin polymerization improve monolayer integrity and reverse plasticity. (A–C) LatA (an actin polymerization inhibitor) and U0126 (a MAPK inhibitor) are the only drugs which reduced cellular velocity (A), TEER (B) and correlation length (C) on the CS-exposed epithelia [cells treated with pathway modulators such as LatA, the actin-polymerizing agent JaspA, U0126, the TGFβ1 neutralizer (1D11), or an antagonist of Wnt signaling pathway (DKK1) and compared to vehicle control]. Data is representative of two donors (three to six inserts per donor). (D) None of the inhibitors restored the CS-induced decrease in basal mRNA expression of the epithelial marker CDH1 . (E–J) The levels of the mesenchymal markers ( CDH2 , VIM , SNAI1 , SNAI2 , ZEB1 and ZEB2 ) were significantly reduced relative to GAPDH in CS-exposed epithelia treated with several pathway modulators (LatA, U0126, 1D11 and DKK1) as analyzed by qPCR. (K) LatA and U0126 treatment reduced mean square displacement (MSD) in CS exposed epithelia. Data is representative of three to six inserts from two donors. (L–O) LatA and U0126 treatment improved TEER in CHBE cells (L), LatA and U0126 treatment decreased cellular velocity in COPD epithelia (CHBE) (M), LatA and U0126 treatment reduced correlation length in CHBE cells (N), and LatA and U0126 treatment improved the height of pseudostratified epithelia on COPD epithelia (CHBE) (O). (P) Representative DIC image from three inserts from one donor taken with a 40× oil objective of CHBE treated with or without LatA or U0126 showing improved monolayer height. Scale bars: 25 µm. (Q) LatA and U0126 treatment reduced the MSD with time in CHBE cells approaching levels similar to that of NHBE. Of note, there is not a significant increase in MSD with time in pEMT-induced NHBE. Data is representative of nine inserts, except for cellular velocity and correlation length (six inserts) and height of pseudostratified epithelia (three inserts) from one donor of CHBE. Graphs are shown with median bars. Statistics determined by Kruskal–Wallis test followed by Dunn's multiple comparison test, with P <0.05 considered statistically significant.

Article Snippet: The NHBE cells at the ALI were exposed to CS for 10 days and simultaneously basolaterally treated with an antagonist of Wnt signaling pathway (recombinant human DKK1 protein, 50 ng/ml, R&D Systems), TGFβ1 neutralizer [TGFβ-1,2,3 monoclonal antibody (1D11), 1.25 μg/ml, Thermo Fisher Scientific], MAPK inhibitor (U0126, 15 μM, Cell Signaling Technology ® ), an inhibitor of actin polymerization (Latrunculin A, 0.625 μM, Sigma-Aldrich) or the actin filament-polymerizing and stabilizing agent (Jasplakinolide A, 0.25 μM, Sigma-Aldrich).

Techniques: Control, Expressing, Marker, Comparison

Journal: Frontiers in Oncology

Article Title: TIPE2 Suppresses Malignancy of Pancreatic Cancer Through Inhibiting TGFβ1 Mediated Signaling Pathway

doi: 10.3389/fonc.2021.680985

Figure Lengend Snippet: TIPE2 inhibited PI3K/AKT and Raf/MEK/ERK signaling pathways triggered by TGFβ1. (A) The total proteins extracted from cells were analyzed for the expression of AKT, ERK and Bax using western blot. The antibodies used were anti-pAKT, anti-AKT, anti-pERK, anti-ERK, anti-Bax and anti-GAPDH. (B) ELISA analysis of TGFβ1 secretion from AsPC-1/vector and AsPC-1/TIPE2 cells. (C) Immunohistochemistry analysis of the TGFβ1 expression in AsPC-1/vector and AsPC-1/TIPE2 tumor tissues. (D) Western blot analysis of the expression of p-TGFBR1 and total TGFBR1 in AsPC-1/vector and AsPC-1/TIPE2 cells. (E) AsPC-1 cells were seeded in 6-well plate and added with or without anti-TGFβ1 antibody or rhTGFβ1 protein. After 48 h incubation, the total proteins extracted from the cultured AsPC-1 cells were analyzed for the expression of AKT and ERK using western blot. The antibodies used were anti-pAKT, anti-AKT, anti-pERK, anti-ERK and anti-GAPDH. Data shown were representative of three independent experiments. Values are presented as means ± SD. ***p < 0.001.

Article Snippet: In AsPC-1 cells, the neutralizing anti-TGFβ1 monoclonal antibody (1 μg/ml, ProteinTech) or 5 ng/ml human recombinant TGFβ1 (ProteinTech) was added for 48 h incubation, respectively.

Techniques: Protein-Protein interactions, Expressing, Western Blot, Enzyme-linked Immunosorbent Assay, Plasmid Preparation, Immunohistochemistry, Incubation, Cell Culture

Journal: Frontiers in Oncology

Article Title: TIPE2 Suppresses Malignancy of Pancreatic Cancer Through Inhibiting TGFβ1 Mediated Signaling Pathway

doi: 10.3389/fonc.2021.680985

Figure Lengend Snippet: TIPE2 suppressed the growth of pancreatic cancer through inhibiting TGFβ1 expression in subcutaneous tumor model. (A) The tumor volume was measured weekly one week after tumor inoculation and the tumor growth curve was calculated. (B, C) The tumors were isolated, weighted and photographed five weeks after tumor cells inoculation. (D) ELISA analysis of TGFβ1 secretion from Panc02/vector and Panc02/TIPE2 cells. (E) Immunohistochemistry analysis of the TGFβ1 expression in Panc02/vector and Panc02/TIPE2 tumor tissues. (F) Western blot analysis of the expression of p-TGFBR1 and total TGFBR1 in Panc02/vector and Panc02/TIPE2 cells. The data shown are the representative of three experiments. Values are presented as means ± SD. *p < 0.05, ***p < 0.001.

Article Snippet: In AsPC-1 cells, the neutralizing anti-TGFβ1 monoclonal antibody (1 μg/ml, ProteinTech) or 5 ng/ml human recombinant TGFβ1 (ProteinTech) was added for 48 h incubation, respectively.

Techniques: Expressing, Isolation, Enzyme-linked Immunosorbent Assay, Plasmid Preparation, Immunohistochemistry, Western Blot

Journal: Immunology and cell biology

Article Title: SjHSP60 induces CD4 + CD25 + Foxp3 + Tregs via TLR4-Mal-drived production of TGF-β in macrophages

doi: 10.1111/imcb.12160

Figure Lengend Snippet: Mφ from S. japonicum-infected mice are sufficient to induce Tregs and exhibit a tolerogenic phenotype characterized by expressing high levels of TGF-β and IL-10. (a, b) Purified CD4+ T cells from normal mice were co-cultured with Mφ from normal or S. japonicum-infected mice for 3 days. CD4+CD25+Foxp3+ Tregs were analyzed by FCM and cells were gated on CD4+ T cells. (c, d) At 13 weeks post-infection, single-cell suspensions of splenocytes or liver cells from S. japonicum-infected mice were stimulated with phorbol myristate acetate and ionomycin in the presence of Golgistop for 6 h. Cells were surface stained with anti-CD11b and anti-F4/80 then intracellularly stained with antibodies against TNF-α, IL-4, IL-6, IL-10, TGF-β1, or isotype antibody and analyzed by FCM. Cells were gated on CD11b+F4/80+ Mφ. FCM plots are representative of three independent experiments. Data are means ± s.d. of triplicate cultures or 5 mice and representative of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: In some co-cultures, a neutralizing antibody to TGFβ1 (5 μg mL −1 ; R&D Systems, Inc. Minneapolis, MN) or an inhibitor of TGF-βRI signaling (20 μmol L −1 ; SB-431542; Sigma-Aldrich) was added.

Techniques: Infection, Expressing, Purification, Cell Culture, Staining

Journal: Immunology and cell biology

Article Title: SjHSP60 induces CD4 + CD25 + Foxp3 + Tregs via TLR4-Mal-drived production of TGF-β in macrophages

doi: 10.1111/imcb.12160

Figure Lengend Snippet: SjHSP60-treated Mφ display a phenotype resembling that of tolerogenic Mφ characterized by expressing high levels of TGF-β and IL-10. (a) Purified Mφ from normal mice were cultured for 2 days in medium alone or in the presence of 0.1 μg mL−1 SjHSP60 or 1 μg mL−1 LPS. The mRNA expression of cytokines in Mφ were determined by qPCR and expressed as fold increases over control. (b) ELISA quantification of cytokines in supernatants of Mφ cultures. Data are means ± s.d. of triplicate cultures and representative of three independent experiments. **P < 0.01.

Article Snippet: In some co-cultures, a neutralizing antibody to TGFβ1 (5 μg mL −1 ; R&D Systems, Inc. Minneapolis, MN) or an inhibitor of TGF-βRI signaling (20 μmol L −1 ; SB-431542; Sigma-Aldrich) was added.

Techniques: Expressing, Purification, Cell Culture, Enzyme-linked Immunosorbent Assay

Journal: Immunology and cell biology

Article Title: SjHSP60 induces CD4 + CD25 + Foxp3 + Tregs via TLR4-Mal-drived production of TGF-β in macrophages

doi: 10.1111/imcb.12160

Figure Lengend Snippet: Production of TGF-β by SjHSP60-Mφ is necessary for conversion of CD4+CD25− T cells into Tregs. (a) At 0, 3, 5, 8 and 13 weeks post-infection, serum TGF-β levels were measured by ELISA. (b) ELISA measurements of TGF-β in serum samples of mice injected with SjHSP60 or PBS. (c) ELISA measurements of cytokines in supernatants of purified CD4+CD25− T cells cultured for 3 days in medium alone or with Mφ that had been unstimulated or exposed to SjHSP60 or LPS for 2 days. (d) Mφ were prestimulated with 0.1 μg mL−1 SjHSP60 or medium for 2 days. Purified CD4+CD25− T cells were cultured for 3 days with medium, SjHSP60, or prestimulated Mφ above. Co-cultures were set up with or without SB-431542 (20 μmol L−1) or neutralizing TGF-β1 antibody (5 μg mL−1). Frequency of CD4+CD25+Foxp3+ Tregs was determined by FCM. FCM plots are representative of three independent experiments with similar results and cells were gated on CD4+ T cells. (e) The bar graph indicates average percentages ± s.d. of Tregs. Data are expressed as means ± s.d. of 6 mice or triplicate cultures and representative of two or three independent experiments. *P < 0.05, **P < 0.01.

Article Snippet: In some co-cultures, a neutralizing antibody to TGFβ1 (5 μg mL −1 ; R&D Systems, Inc. Minneapolis, MN) or an inhibitor of TGF-βRI signaling (20 μmol L −1 ; SB-431542; Sigma-Aldrich) was added.

Techniques: Infection, Enzyme-linked Immunosorbent Assay, Injection, Purification, Cell Culture

Journal: Immunology and cell biology

Article Title: SjHSP60 induces CD4 + CD25 + Foxp3 + Tregs via TLR4-Mal-drived production of TGF-β in macrophages

doi: 10.1111/imcb.12160

Figure Lengend Snippet: SjHSP60-triggered TGF-β production in Mφ is TLR4-dependent. (a, b) Purified Mφ from TLR2−/−, TLR4−/− mice or control WT littermates were stimulated with or without 0.1 μg mL−1 SjHSP60 for 2 days. In some cultures, purified Mφ from control littermates were pretreated with medium alone, or with 20 μg mL−1 of anti-TLR2, anti-TLR4 blocking or isotype-matched antibodies for 1 h at 4°C. After stimulation, TGF-β production was detected by ELISA. Data are means ± s.d. of triplicate cultures and representative of three independent experiments. **P < 0.01.

Article Snippet: In some co-cultures, a neutralizing antibody to TGFβ1 (5 μg mL −1 ; R&D Systems, Inc. Minneapolis, MN) or an inhibitor of TGF-βRI signaling (20 μmol L −1 ; SB-431542; Sigma-Aldrich) was added.

Techniques: Purification, Blocking Assay, Enzyme-linked Immunosorbent Assay

Journal: Immunology and cell biology

Article Title: SjHSP60 induces CD4 + CD25 + Foxp3 + Tregs via TLR4-Mal-drived production of TGF-β in macrophages

doi: 10.1111/imcb.12160

Figure Lengend Snippet: SjHSP60-triggered TGF-β production and Treg conversion are MyD88-independent. (a, b) MyD88+/+ or MyD88−/− Mφ were stimulated with 0.1 μg mL−1 SjHSP60 for 2 days. TGF-β mRNA expression was detected by qPCR and expressed as fold increases over unstimulated MyD88+/+ Mφ (a). Culture supernatants were collected for determining TGF-β production by ELISA (b). (c, d) Purified CD4+CD25− T cells were co-cultured with MyD88+/+ or MyD88−/− Mφ prestimulated with 0.1 μg mL−1 SjHSP60 or medium. After 3 days, percentages of CD4+CD25+Foxp3+ Tregs were analyzed by FCM. FCM plots are representative of three independent experiments with consistent results and cells were gated on CD4+ T cells. The bar graph indicates average percentages ± s.d. of Tregs. Data are means ± s.d. of triplicate cultures and representative of two or three independent experiments. **P < 0.01.

Article Snippet: In some co-cultures, a neutralizing antibody to TGFβ1 (5 μg mL −1 ; R&D Systems, Inc. Minneapolis, MN) or an inhibitor of TGF-βRI signaling (20 μmol L −1 ; SB-431542; Sigma-Aldrich) was added.

Techniques: Expressing, Enzyme-linked Immunosorbent Assay, Purification, Cell Culture

Journal: Immunology and cell biology

Article Title: SjHSP60 induces CD4 + CD25 + Foxp3 + Tregs via TLR4-Mal-drived production of TGF-β in macrophages

doi: 10.1111/imcb.12160

Figure Lengend Snippet: SjHSP60-triggered TGF-β production and Treg conversion are Mal-dependent. (a) Purified Mφ from MyD88−/− mice or control WT littermates were cultured with or without 0.1 μg mL−1 SjHSP60 for 2 days. Mal mRNA levels were determined by qPCR and expressed as fold increases over unstimulated MyD88+/+ Mφ. (b, c) Effect of specific siRNA on endogenous Mal expression in RAW264.7 cells was analyzed by qPCR (b) and Western blot (c). (d, e) RAW264.7 cells transfected with Mal siRNA or control siRNA were stimulated with 0.1 μg mL−1 of SjHSP60. After 2 days, TGF-β levels in supernatants were detected by ELISA (e), while cells were washed and co-cultured with purified CD4+CD25− T cells for three additional days. Percentages of CD4+CD25+Foxp3+ Tregs in co-cultures were measured by FCM and cells were gated on CD4+ T cells (e). (f) The bar graph indicates average percentages ± s.d. of Tregs. Western blots and FCM plots are representative of three independent experiments with consistent results. Data are means ± s.d. of triplicate cultures and representative of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: In some co-cultures, a neutralizing antibody to TGFβ1 (5 μg mL −1 ; R&D Systems, Inc. Minneapolis, MN) or an inhibitor of TGF-βRI signaling (20 μmol L −1 ; SB-431542; Sigma-Aldrich) was added.

Techniques: Purification, Cell Culture, Expressing, Western Blot, Transfection, Enzyme-linked Immunosorbent Assay

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Neurotrophin and TGFβ signaling. ( A ) Simplified scheme showing neurotrophin and Smad-dependent TGFβ signaling pathways. ( B ) Quantitative real time RT-PCR (qPCR) of Ngf mRNA expression in Tgfbr2 Δoc and Smad7 Δoc -deficient and in their respective control littermate’s retinae. Data are mean ± SEM, n ≥ 5, * p = 0.0214 ( Tgfbr2 Δoc ), * p = 0.0366 ( Smad7 Δoc ). Expression is normalized to Gapdh. ( C ) QPCR analyses of RNA samples from neuronal cells (RGC-5 cells) treated with TGFβ2 (1 and 3 ng) or in combination with SIS3 (1 µM + 3 ng TGFβ2), an inhibitor of Smad3 phosphorylation. Ngf mRNA expression significantly increases following TGFβ treatment and its expression reverses to control levels if TGFβ is inhibited. Data are mean ± SEM, n ≥ 4, * p = 0.0119 (3 ng TGFβ2), ** p = 0.0059 (SIS3 + TGFβ2). Expression is normalized to Gapdh . ( D ) NGF immunoreactivity (red) in the retinae of Tgfbr2 Δoc , control and Smad7 Δoc -deficient mice at postnatal day 10. Nuclei are DAPI stained (blue). In the retina of the Smad7 Δoc -deficient mouse, NGF immunoreactivity is considerably stronger with distinct preference for the perikarya (arrowheads) in the ganglion cell, inner nuclear and outer plexiform layer. In contrast labeling of the perikarya in the ganglion cell, inner nuclear and outer plexiform layer is less frequent and intense in the control retina and rarely observed in the Tgfbr2 Δoc retina. The original data from ( B – D ), that we show in a slightly modified representation here, have been published in . NGF = nerve growth factor, BDNF = brain-derived neurotrophic factor, NT-3 = neurotrophin 3, proNT = pro Neurotrophin, mNT = mature neurotrophin, TGFβ = transforming growth factor β, Trk A–C = tropomyosin receptor kinase A–C, p75 = p75 neurotrophin receptor, TGFβRI/II = transforming growth factor beta receptor 1/2, PLC y = phospholipase C gamma, PKC = protein kinase C, MAPK = mitogen-activated protein kinase, TFs = transcription factors, PI3-K = phosphoinositide 3-kinase, NF-kB = nuclear factor kappa-light-chain-enhancer of activated B cells, JNK = c-Jun N-terminal kinase, GCL = ganglion cell layer, INL = inner nuclear layer, ONL = outer nuclear layer.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Protein-Protein interactions, Quantitative RT-PCR, Expressing, Control, Phospho-proteomics, Staining, Labeling, Modification, Derivative Assay

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Neurotrophin and TGFβ signaling in myocardial infarction (MI). Scheme illustrating the three phases following MI that comprise the inflammatory, proliferative, and maturation phase. During each phase, multiple cellular processes occur, with the ultimate goal of healing the affected tissue. Neurotrophins and TGFβ are upregulated following MI and modulate processes in the inflammatory, proliferative, and maturation phase. TGFβ = transforming growth factor β, NT = neurotrophins.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques:

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Angiogenic properties of neurotrophin and TGFβ signaling. Scheme showing the interplay of neurotrophins, TGFβ signaling, and endothelial cells in the retina. TGFβ mediates upregulation of neurotrophins in the retina, which promote angiogenesis either by direct binding to Trk receptors on endothelial cells, or by inducing VEGF expression and subsequent activation of VEGFR2. TGFβ = transforming growth factor β, VEGF = vascular endothelial growth factor, VEGFR2 = vascular endothelial growth factor receptor 2, Trk = tropomyosin receptor kinase.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Binding Assay, Expressing, Activation Assay

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Deletion of TGFβ signaling results in retinal and choroidal neovascularization. ( A ) Light-sheet fluorescence microscopy of cleared eyes of 6-week-old lectin-injected Tgfbr2 Δeye mice and a control littermate. The control mouse shows an essentially regular arborized retinal vasculature. The Tgfbr2 Δeye mice have an irregular arrangement of the retinal plexus and develop choroidal neovascularization forming anastomoses between retinal and choroidal vessels (arrows). ( B ) FITC-dextran (green) perfused retinal meridional sections of 6-week-old Tgfbr2 ΔEC mice and a control littermate. White arrows point toward tracer leakage in the retinal pigment epithelium (RPE; middle panel) and choroidal neovascularization (right panel) invading the RPE and subretinal space. Nuclei are DAPI stained (blue). ( C ) Meridional section of a 6-week-old FITC-dextran (green) perfused Tgfbr2 Δeye retina shows neovascularization into the vitreous (white arrows), similar to what can be observed in patients suffering from proliferative diabetic retinopathy. Nuclei are DAPI stained (blue). The original data which we show in a slightly modified representation here, have been published in [ , ]. GCL = ganglion cell layer, INL = inner nuclear layer, ONL = outer nuclear layer, RPE = retinal pigment epithelium.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Fluorescence, Microscopy, Injection, Control, Staining, Modification

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: Roles of TGFβ and neurotrophins in recovery from ischemic stroke. Ischemic stroke is induced by a thrombus occluding a brain artery, which impairs blood supply distal to the occlusion. Neurons within the infarct core (<12 mL blood/100 g tissue/min) die rapidly and become necrotic. Neurons within the penumbra (12–22 mL blood/100 g tissue/min) can recover depending on timely reperfusion and the action of different neuroprotective factors such as TGFβ and neurotrophins. Neurons within the oligemia (22–35 mL blood/100 g tissue/min) usually recover completely from the mild ischemia, irrespective of treatment. Gliosis and neuroinflammation are a response to the tissue damage and regulated by TGFβ and neurotrophins. They can be both beneficial and detrimental to post-stroke recovery and neuronal survival. TGFβ = transforming growth factor β, NGF = nerve growth factor; BDNF = brain-derived neurotrophic factor.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Derivative Assay

Journal: Biomolecules

Article Title: TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain

doi: 10.3390/biom11091360

Figure Lengend Snippet: The heart-brain and brain-retina axis. Neurotrophins (NT) and TGFβ are upregulated following ischemic insults (red lightning symbol) to the heart, retina, and brain. Following myocardial infarction, the heart-brain axis is activated by transmitting mechano- and chemo-sensitive information through cardiac afferent fibers (dotted arrow) to the brain, which responds by releasing BDNF to the bloodstream. Thus, BDNF promotes recovery from myocardial infarction by endocrine and paracrine actions. TGFβ directly affects repair processes following ischemic insults. Moreover, it has the ability to increase the expression of NT. Additionally, retrograde transport of neurotrophins is essential for survival of retinal ganglion cells. This close relationship could be defined as a brain-retina axis. TGFβ = transforming growth factor β, NT = neurotrophin, BDNF = brain-derived neurotrophic factor.

Article Snippet: Systemic inhibition of TGFβ signaling by administering a neutralizing antibody against TGFβ 1–3 (clone 1D11, Genzyme) starting on day one of experimentally induced MI (and 3 x/week thereafter) confirmed the detrimental effects of systemic TGFβ inhibition as all anti-TGFβ-treated animals died within 5 days, whereas control antibody-treated mice showed the expected 40% mortality rate [ ].

Techniques: Expressing, Derivative Assay