Journal: The Cell Surface

Article Title: Pap1 is an adhesin involved in the interaction of Sporothrix schenckii and Sporothrix brasiliensis with the host

doi: 10.1016/j.tcsw.2025.100164

Figure Lengend Snippet: Cytokine stimulation by human peripheral blood mononuclear cells. Yeast-like cells and human peripheral blood mononuclear cells were coincubated for 24 h, and the secreted cytokines were quantified by ELISA. Panels A , C , and E are results generated with S. schenckii yeast-like cells (WT, 1099–18 ATCC MYA 4821 strain), while panels B , D , and F are results obtained with S. brasiliensis strains (WT, 5110 ATCC MYA 4823 strain). None, human cells preincubated with 5 μg mL −1 polymyxin B; Anti-MR, human cells preincubated with 5 μg mL −1 polymyxin B and 10 μg mL −1 anti-mannose receptor antibody. Anti-TLR4, human cells preincubated with 5 μg mL −1 polymyxin B and 10 μg mL −1 anti-TLR4. Data are means ± SD obtained with samples from eight donors, each assayed in duplicate wells. Results were analyzed with Dunnett's test and then the Mann-Whitney U test. * P < 0.05 when compared to strains WT, HSS67, or HSS68 (panels A , C , and E ). * P < 0.05 when compared to strains WT, HSB28, or HSB29 (panels B , D , and F ). † P < 0.05 when compared to the “None” group from the same strain.

Article Snippet: When required, the human cells were pre-incubated for 1 h at 37 °C and 5 % (v/v) CO 2 with one of the following immune receptor antagonists: 10 μg mL −1 of anti-mannose receptor (MR) (Thermo-Fisher Scientific, MA5–44033), or 10 μg mL −1 anti-TLR4 antibody (Santa Cruz Biotechnology, Dallas, TX, USA sc-293,072).

Techniques: Enzyme-linked Immunosorbent Assay, Generated, MANN-WHITNEY

Journal: The Cell Surface

Article Title: Pap1 is an adhesin involved in the interaction of Sporothrix schenckii and Sporothrix brasiliensis with the host

doi: 10.1016/j.tcsw.2025.100164

Figure Lengend Snippet: Phagocytosis of Sporothrix schenckii and Sporothrix brasiliensis PAP1 -silenced strains. Yeast-like cells were labeled with Acridine Orange and used to interact with human monocyte-derived macrophages for 2 h at 37 °C and 5 % (v/v) CO 2 . Then, macrophages were collected and analyzed by flow cytometry. Macrophages that were interacting with at least one red fluorescent yeast-like cell were included in the analysis. None, human cells preincubated with 5 μg mL-1 polymyxin B. Anti-MR, human cells preincubated with 5 μg mL −1 polymyxin B and 10 μg mL −1 anti-mannose receptor antibody. Anti-TLR4, human cells preincubated with 5 μg mL −1 polymyxin B and 10 μg mL −1 anti-TLR4. Panel A , results generated with S. schenckii yeast-like cells (WT, 1099–18 ATCC MYA 4821 strain); while in panel B are results obtained with S. brasiliensis strains (WT, 5110 ATCC MYA 4823 strain). Data are means ± SD obtained with samples from eight donors, each assayed in duplicate wells. Results were analyzed with Dunnett's test and then the Mann-Whitney U test. * P < 0.05 when compared to strains WT, HSS67, or HSS68 (panel A ). * P < 0.05 when compared to strains WT, HSB28, or HSB29 (panel B ). † P < 0.05 when compared to the “None” group from the same strain. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: When required, the human cells were pre-incubated for 1 h at 37 °C and 5 % (v/v) CO 2 with one of the following immune receptor antagonists: 10 μg mL −1 of anti-mannose receptor (MR) (Thermo-Fisher Scientific, MA5–44033), or 10 μg mL −1 anti-TLR4 antibody (Santa Cruz Biotechnology, Dallas, TX, USA sc-293,072).

Techniques: Labeling, Derivative Assay, Flow Cytometry, Generated, MANN-WHITNEY

Journal: The Cell Surface

Article Title: Pap1 is an adhesin involved in the interaction of Sporothrix schenckii and Sporothrix brasiliensis with the host

doi: 10.1016/j.tcsw.2025.100164

Figure Lengend Snippet: Cytokine stimulation by human monocyte-derived macrophages. Yeast-like cells and monocyte-derived macrophages were coincubated for 24 h, and the secreted cytokines were quantified by ELISA. Panels A and C are results generated with S. schenckii yeast-like cells (WT, 1099–18 ATCC MYA 4821 strain); while panels B and D are results obtained with S. brasiliensis strains (WT, 5110 ATCC MYA 4823 strain). None, human cells preincubated with 5 μg mL −1 polymyxin B. Anti-MR, human cells preincubated with 5 μg mL −1 polymyxin B and 10 μg mL −1 anti-mannose receptor antibody. Anti-TLR4, human cells preincubated with 5 μg mL −1 polymyxin B and 10 μg mL −1 anti-TLR4. Data are means ± SD obtained with samples from eight donors, each assayed in duplicate wells. Results were analyzed with Dunnett's test and then the Mann-Whitney U test. * P < 0.05 when compared to strains WT, HSS67, or HSS68 (panels A and C ). * P < 0.05 when compared to strains WT, HSB28, or HSB29 (panels B and D ). cells. † P < 0.05 when compared to the “None” group from the same strain.

Article Snippet: When required, the human cells were pre-incubated for 1 h at 37 °C and 5 % (v/v) CO 2 with one of the following immune receptor antagonists: 10 μg mL −1 of anti-mannose receptor (MR) (Thermo-Fisher Scientific, MA5–44033), or 10 μg mL −1 anti-TLR4 antibody (Santa Cruz Biotechnology, Dallas, TX, USA sc-293,072).

Techniques: Derivative Assay, Enzyme-linked Immunosorbent Assay, Generated, MANN-WHITNEY

Journal: Ultrasonics Sonochemistry

Article Title: Ultrasound-assisted extraction optimization of Fructus Tribuli polysaccharides: How stir-frying processing alters structures and enhances antihypertensive efficacy

doi: 10.1016/j.ultsonch.2026.107829

Figure Lengend Snippet: Effect of FP and SFP on the TLR4/MyD88 signaling in blood vessels. (A) Representative images from immunohistochemical staining of TLR4 in blood vessels (×200). (B, C, E) Western blotting to determine the levels of TLR4, MyD88, NFκB p65 and its phosphorylation, IκBα and its phosphorylation, and IKKβ and its phosphorylation in blood vessels. (D) Changes in serum TNF-α and IL-6 levels. (F) Relative expression of TLR4, MyD88, NFκB p65, IκBα, and IKKβ mRNA. Compared with the WKY group, # p < 0.05, ## p < 0.01; compared with the SHR group, * p < 0.05, ** p < 0.01; compared with the FP group, ▲ p < 0.05, ▲▲ p < 0.01, n = 3.

Article Snippet: TLR4 polyclonal antibody (19811–1-AP), GAPDH (10494–1-AP) antibody, goat anti-mouse immunoglobulin (Ig)G (H + L) (SA00001-1), and goat anti-rabbit IgG (H + L) (SA00001-2) were purchased from Proteintech Group (Wuhan, China).

Techniques: Immunohistochemical staining, Staining, Western Blot, Phospho-proteomics, Expressing

Journal: Ultrasonics Sonochemistry

Article Title: Ultrasound-assisted extraction optimization of Fructus Tribuli polysaccharides: How stir-frying processing alters structures and enhances antihypertensive efficacy

doi: 10.1016/j.ultsonch.2026.107829

Figure Lengend Snippet: Effect of FP and SFP on the TLR4/MyD88 signaling in blood vessels. (A) Representative images from immunohistochemical staining of TLR4 in blood vessels (×200). (B, C, E) Western blotting to determine the levels of TLR4, MyD88, NFκB p65 and its phosphorylation, IκBα and its phosphorylation, and IKKβ and its phosphorylation in blood vessels. (D) Changes in serum TNF-α and IL-6 levels. (F) Relative expression of TLR4, MyD88, NFκB p65, IκBα, and IKKβ mRNA. Compared with the WKY group, # p < 0.05, ## p < 0.01; compared with the SHR group, * p < 0.05, ** p < 0.01; compared with the FP group, ▲ p < 0.05, ▲▲ p < 0.01, n = 3.

Article Snippet: TLR4 antibody (sc-293072) was purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA).

Techniques: Immunohistochemical staining, Staining, Western Blot, Phospho-proteomics, Expressing

Journal: Journal of Advanced Research

Article Title: Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation

doi: 10.1016/j.jare.2025.07.013

Figure Lengend Snippet: Podocyte-specific TLR4 deletion mitigated STZ-induced DKD, podocyte injury, and proteinuria in mice. (A) Schematic description of the strategy for generating STZ-induced diabetic mouse model in NPHS2 -Cre; TLR4 fl/fl ( TLR4 CKO) mice and in TLR4 fl/fl mice (CTL). (B) Monthly monitoring of plasma glucose levels in mice. Data are presented as mean ± SD. ** P < 0.01 vs. CTL-NC; ## P < 0.01 vs. CKO-NC. (C) Monthly monitoring of body weight in mice. Data are presented as mean ± SD. ** P < 0.01 vs. CTL-NC; # P < 0.05 vs. CKO-NC; # # P < 0.01 vs. CKO-NC; # ### P < 0.01 vs. CTL-STZ. (D) Representative images of PAS and MASSON staining of the glomeruli in mice at 12 and 16 weeks. Scale bar, 20 μm ( n = 8). (E) Representative images of HE staining of the kidney in mice at 12 and 16 weeks. Scale bar, 50 μm ( n = 8). (F) Representative IF images of the expression of SD proteins p-cadherin and synaptopodin in glomeruli at 12 and 16 weeks. Scale bar, 20 μm ( n = 8). (G) The expression of a mesenchymal marker desmin was detected in renal tissues from mice at 12 and 16 weeks by western blot analysis. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; # P < 0.05; ## P < 0.05 ( n = 8). (H) Representative images of TEM in podocyte ultrastructural alterations in mice. FPs effacement (blue arrow), ER dilation (red arrow) and GBM thickness were observed in podocytes in STZ-induced CTL diabetic mice, and were attenuated in TLR4 CKO diabetic mice at 16 weeks. Scale bar, 1 μm ( n = 8). (I) Determination of proteinuria in mice. Data are presented as mean ± SD. ** P < 0.01 vs. CTL-NC; # P < 0.05 vs. CKO-NC; # # P < 0.01 vs. CKO-NC; # ## P < 0.05 vs. CTL-STZ; # ### P < 0.01 vs. CTL-STZ.

Article Snippet: NPHS2 -Cre mice and TLR4 floxed mice (C57BL/6n background) were purchased from Cyagen Biosciences (Guangzhou, China).

Techniques: Clinical Proteomics, Staining, Expressing, Marker, Western Blot

Journal: Journal of Advanced Research

Article Title: Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation

doi: 10.1016/j.jare.2025.07.013

Figure Lengend Snippet: Activation of TLR4/MyD88/PKCδ/SHP-1 signaling cascade was involved in hyperglycemic podocyte damage in vivo and in vitro . (A) The protein levels of TLR4 were determined in renal tissues from mice at 12 and 16 weeks by western blot analysis. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; # P < 0.05 ( n = 8). (B) Representative western blot of the expression of MyD88, p-PKCδ (Y311), PKCδ and SHP-1 in renal cortex from mice at 12 and 16 weeks. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; # P < 0.05; ## P < 0.01; ### P < 0.01 ( n = 8). (C) Representative double IF staining of glomerular SHP-1 and synaptopodin expression in mice at 16 weeks. Scale bar, 20 μm ( n = 8). (D) The expression of TLR4, MyD88, p-PKCδ, PKCδ and SHP-1 in cultured mouse podocytes from treatments of LG or HG for 48 h with or without transfection of TLR4, MyD88 or scrambled shRNAs. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; ## P < 0.01; ### P < 0.01; #### P < 0.01 ( n = 3 independent experiments). (E) IF staining of podocyte proteins p-cadherin and synaptopodin after LG or HG stimulation for 48 h with or without transfection of TLR4, PKCδ, MCP-1 or scrambled shRNAs, or pretreatment of 4-PBA. Magnification 400 × . ( n = 3 independent experiments). (F) Determination of SD protein podocin and injury marker desmin in podocytes treated with LG or HG for 48 h with or without transfection of TLR4, MyD88 or scrambled shRNAs. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; ### P < 0.01; #### P < 0.01 ( n = 3 independent experiments).

Article Snippet: NPHS2 -Cre mice and TLR4 floxed mice (C57BL/6n background) were purchased from Cyagen Biosciences (Guangzhou, China).

Techniques: Activation Assay, In Vivo, In Vitro, Western Blot, Expressing, Staining, Cell Culture, Transfection, Marker

Journal: Journal of Advanced Research

Article Title: Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation

doi: 10.1016/j.jare.2025.07.013

Figure Lengend Snippet: Hyperglycemia triggered PKCδ activation and subsequent binding to downstream SHP-1 following TLR4/MyD88 signaling to induce podocyte damage. (A) Determination of expression of p-PKCδ, PKCδ and SHP-1 in cultured podocytes from treatments of HG for 48 h with or without transfection of PKCδ, SHP-1 or scrambled shRNAs, or pretreatment of 4-PBA. P values were determined by one-way ANOVA and data are presented as mean ± SD. ** P < 0.01; *** P < 0.01; **** P < 0.001; ## P < 0.01; #### P < 0.01 ( n = 3 independent experiments). (B) The expression of podocin and desmin in podocytes treated with HG for 48 h with or without transfection of PKCδ, SHP-1 or scrambled shRNAs, or pretreatment of 4-PBA. P values were determined by one-way ANOVA and data are presented as mean ± SD. ** P < 0.01; ## P < 0.01 ( n = 3 independent experiments). (C) The representative western blot to show the expression of TLR4 and MyD88 in podocytes after HG stimulation for 48 h with or without transfection of PKCδ, SHP-1 or scrambled shRNAs, or pretreatment of 4-PBA. Data are presented as mean ± SD. P values were determined by one-way ANOVA and data are presented as mean ± SD; P > 0.05 ( n = 3 independent experiments). (DF) Surface diagram of the docking model and their interfacing residues between MyD88 and PKCδ (D) (MyD88, purple; PKCδ, yellow; hydrogen bonds, dotted line), and between PKCδ and SHP-1 (F) (PKCδ, yellow; SHP-1, blue; hydrogen bonds, dotted line). (EG) CO-IP analysis of the interaction between MyD88 and PKCδ (E), and between PKCδ and SHP-1 (G) in podocytes under HG condition in vitro . ( n = 3 independent experiments).

Article Snippet: NPHS2 -Cre mice and TLR4 floxed mice (C57BL/6n background) were purchased from Cyagen Biosciences (Guangzhou, China).

Techniques: Activation Assay, Binding Assay, Expressing, Cell Culture, Transfection, Western Blot, Co-Immunoprecipitation Assay, In Vitro

Journal: Journal of Advanced Research

Article Title: Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation

doi: 10.1016/j.jare.2025.07.013

Figure Lengend Snippet: TLR4/MyD88/PKCδ/SHP-1 signaling cascade induced podocyte damage through regulating ER stress in DKD and podocyte damage. (A) The protein levels of ER stress markers BIP, sXBP-1, ATF4 and ATF6 were determined in renal tissues from mice at 12 and 16 weeks by western blot. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; # P < 0.05; ## P < 0.01; ### P < 0.01 ( n = 8). (B) Representative double IF staining of the expression ATF4 and podocyte marker synaptopodin in mice at 16 weeks. Scale bar, 20 μm ( n = 8). (C) Representative western blot to assess the levels of ER stress markers BIP, sXBP-1, ATF4 and ATF6 in cultured mouse podocytes from treatments of LG or HG for 48 h with or without transfection of TLR4, MyD88 or scrambled shRNAs. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; ### P < 0.01; ### P < 0.01 ( n = 3 independent experiments). (D) ER morphological alterations and ER stress illustrated by ER-tracker staining in podocytes treated with LG or HG for 48 h with or without transfection of TLR4, PKCδ, or MCP-1 shRNAs, or pretreatment of 4-PBA. Scale bar, 10 μm. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; ## P < 0.01; # P < 0.05 ( n = 3 independent experiments). (E) Representative western blot to detect the expression of ER stress proteins BIP, sXBP-1, ATF4 and ATF6 in cultured podocytes after HG stimulation for 48 h with or without transfection of PKCδ, SHP-1 or scrambled shRNAs, or pretreatment of 4-PBA. P values were determined by one-way ANOVA and data are presented as mean ± SD. ** P < 0.01; *** P < 0.01; **** P < 0.01; ## P < 0.01; ### P < 0.01; #### P < 0.01 ( n = 3 independent experiments).

Article Snippet: NPHS2 -Cre mice and TLR4 floxed mice (C57BL/6n background) were purchased from Cyagen Biosciences (Guangzhou, China).

Techniques: Western Blot, Staining, Expressing, Marker, Cell Culture, Transfection

Journal: Journal of Advanced Research

Article Title: Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation

doi: 10.1016/j.jare.2025.07.013

Figure Lengend Snippet: TLR4/MyD88/PKCδ/SHP-1 signaling-dependent ER stress stimulated MCP-1 production via enhanced transcription activity by ATF4 binding to its promoter in hyperglycemic podocytes. (A) The altered expression of MCP-1 in renal tissue from mice at 12 and 16 weeks by western blot. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; # P < 0.05; ## P < 0.01 ( n = 8 samples). (B) Representative western blot to assess the levels of MCP-1 in cultured mouse podocytes from treatments of LG or HG for 48 h with or without transfection of TLR4, MyD88 or scrambled shRNAs. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; ### P < 0.01 ( n = 3 independent experiments). (C) Representative western blot to show the expression of MCP-1 in podocytes after HG stimulation for 48 h with or without transfection of PKCδ, SHP-1 or scrambled shRNAs, or pretreatment of 4-PBA. P values were determined by one-way ANOVA and data are presented as mean ± SD. ** P < 0.01; *** P < 0.01; ### P < 0.01 ( n = 3 independent experiments). (DE) The expression of MCP-1 by western blot (D), and ER stress markers BIP, sXBP-1, ATF4 and ATF6 (E) after HG stimulation for 48 h with or without MCP-1 or scrambled shRNA transfection. P values were determined by one-way ANOVA and data are presented as mean ± SD. ## P < 0.01; #### P < 0.01 ( n = 3 independent experiments). (F) Schematic description of primers spanning the distal, medial, and proximal regions of the MCP-1 promoter, encompassing predicted binding sites in the present study. (GH) ChIP analysis using anti-ATF4 or anti-IgG antibodies were performed either in cultured mouse podocytes after LG or HG treatment for 48 h (G), or HG stimulation with transfection of TLR4, PKCδ, MCP-1 or scrambled shRNA, or pretreatment of 4-PBA (H). Real-time PCR was used for the detection of the ChIP signals. P values were determined by Student’s t -test, or by one-way ANOVA, and data are presented as mean ± SD. * P < 0.05; ** P < 0.01; **** P < 0.01; #### P < 0.01 ( n = 3 independent experiments). (I) Determination of ATF4 nuclear accumulation in podocytes under LG or HG conditions by western blot. P values were determined by Student’s t -test and data are presented as mean ± SD. ** P < 0.01; ## P < 0.01 ( n = 3 independent experiments). (J) Assessment of nuclear ATF4 protein levels in cultured podocytes transfected with TLR4, PKCδ, MCP-1 or scrambled shRNAs, or pretreated with 4-PBA under HG conditions for 48 h. P values were determined by one-way ANOVA and data are presented as mean ± SD. * P < 0.05; * P < 0.01 ( n = 3 independent experiments).

Article Snippet: NPHS2 -Cre mice and TLR4 floxed mice (C57BL/6n background) were purchased from Cyagen Biosciences (Guangzhou, China).

Techniques: Activity Assay, Binding Assay, Expressing, Western Blot, Cell Culture, Transfection, shRNA, Real-time Polymerase Chain Reaction

Journal: Journal of Advanced Research

Article Title: Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation

doi: 10.1016/j.jare.2025.07.013

Figure Lengend Snippet: Blockade of TLR4/MyD88/PKCδ/SHP-1 signaling attenuated podocyte cytoskeletal remodeling and inflammation, and macrophage recruitment and infiltration through decreasing ER stress and MCP-1 production under hyperglycemic conditions. (A) Assessment of podocyte migration by transwell assay in cultured podocytes treated with LG or HG for 48 h with or without transfection of TLR4, PKCδ, MCP-1 or scrambled shRNAs, or pretreatment of 4-PBA. P values were determined by one-way ANOVA and data are presented as mean ± SD. **** P < 0.01; ## P < 0.01; ### P < 0.01; #### P < 0.01 ( n = 3 independent experiments). (B) Representative IF images by phalloidin staining to illustrate F-actin distribution and cytoskeletal remodeling in cultured podocytes treated with LG or HG for 48 h with or without transfection of TLR4, PKCδ, MCP-1 or scrambled shRNAs, or pretreatment of 4-PBA. Magnification 400 × . ( n = 3 independent experiments). (C) Assessment of the secretion of inflammatory factors IL-6 and IL-1β in podocytes treated with LG or HG for 48 h with or without transfection of TLR4, PKCδ, or scrambled shRNAs, or pretreatment of 4-PBA. P values were determined by one-way ANOVA followed by Tukey’s multiple comparisons test and data are presented as mean ± SD. **** P < 0.01; # P < 0.05; ## P < 0.01; ### P < 0.01 ( n = 3 independent experiments). (D) IHC staining using anti-f4/80 antibodies to illustrate macrophage infiltration in the glomeruli from mice at 16 weeks (Red arrow). Scale bar, 20 μm. ( n = 8) (E) The model diaphragm of podocyte-macrophage co-culture. (F) Representative images and assessment of macrophage migration by transwell assay after co-cultured with podocytes treated with LG or HG for 48 h with or without transfection of TLR4, PKCδ, MCP-1 or scrambled shRNAs, or pretreatment of 4-PBA. Magnification 400 × . P values were determined by one-way ANOVA followed by Tukey’s multiple comparisons test and data are presented as mean ± SD. **** P < 0.01; ## P < 0.01; ### P < 0.01 ( n = 3 independent experiments).

Article Snippet: NPHS2 -Cre mice and TLR4 floxed mice (C57BL/6n background) were purchased from Cyagen Biosciences (Guangzhou, China).

Techniques: Migration, Transwell Assay, Cell Culture, Transfection, Staining, Immunohistochemistry, Co-Culture Assay

Journal: Journal of Advanced Research

Article Title: Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PKCδ/SHP-1-dependent ER stress and relieving podocyte damage and inflammation

doi: 10.1016/j.jare.2025.07.013

Figure Lengend Snippet: Schematic diaphragm of TLR4/MyD88/PKCδ/SHP-1 signaling in podocytes in exposure of hyperglycemia. Upon the stimuli of hyperglycemia, TLR4/MyD88 signaling was activated in glomerular podocyte; and PKCδ was then phosphorylated and bound to SHP-1 to provoke downstream ER stress, leading to nuclear translocation of ATF4 and enhanced transcriptional activity of MCP-1, which exacerbated damage to SD proteins and disruption of the cytoskeletal structure, increased cell motility, promoted inflammation in podocytes, and finally induced local macrophage migration and infiltration.

Article Snippet: NPHS2 -Cre mice and TLR4 floxed mice (C57BL/6n background) were purchased from Cyagen Biosciences (Guangzhou, China).

Techniques: Translocation Assay, Activity Assay, Disruption, Migration