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Image Search Results
Journal: Cell metabolism
Article Title: A WISP1 antibody inhibits MRTF signaling to prevent the progression of established liver fibrosis.
doi: 10.1016/j.cmet.2022.07.009
Figure Lengend Snippet: Figure 2. Reverse translational analysis links WISP1 and MRTF-cytoskeleton signaling in liver fibrosis (A) Correlation of WISP1 expression with MRTF signature eigengene in fibrotic livers. (B) WISP1 mRNA levels in human livers at distinct fibrosis stage as indicated (MATAVIR F0, n = 12; F1, n = 15; F2, n = 15; F3, n = 14; F4, n = 13). (C) Correlation between WISP1 mRNA levels and liver fibrosis score in human patients described in (B). p value is calculated using Pearson test. (D) WISP1 protein levels in serum samples from patients with NASH (F3/4, n = 32) and healthy volunteers (HV, n = 16). (E) Boxplot showing the percent of cells expressing WISP1 in human cirrhotic livers, split by major cell population, with individual samples shown as diamonds (scRNA-seq data from GEO: GSE136103). (F) Representative images of WISP1 and ACTA2 immunofluorescence in healthy and fibrotic liver sections (scale bars, 25 mm) and quantification of percentage of WISP1/ACTA2 double positive cells. (G) Representative western blots of nuclear (top panel) and total MRTFA and MRTFB (bottom panel) in HSCs stimulated with human WISP1 (hWISP1). Yin Yang 1 (YY1) is a loading control for nuclear fractions. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a loading control for whole-cell lysates. (H) Cytoskeleton gene expression in HSCs transfected with MRTFA and MRTFB or control siRNA in the presence or absence of hWISP1, n = 3 biological replicates. (I and J) Live-cell imaging (I) and quantification (J) of HSC migration toward FBS in the presence or absence of hWISP1. Stellate cells that migrated through pores to bottom surface of transwell were highlighted in yellow. n = 4 biological replicates.
Article Snippet: REAGENT or
Techniques: Expressing, Western Blot, Control, Gene Expression, Transfection, Live Cell Imaging, Migration
Journal: Cell metabolism
Article Title: A WISP1 antibody inhibits MRTF signaling to prevent the progression of established liver fibrosis.
doi: 10.1016/j.cmet.2022.07.009
Figure Lengend Snippet: Figure 3. Wisp1 is required for liver fibrosis progression, but not initiation, in CCl4 model (A) Top 20 GO biological processes enriched in the upregulated genes in livers from 6-week CCl4 model. (B) Heatmap of Wisp1 and cytoskeleton gene expression in livers from 6-week CCl4 model, n = 6 mice/group. (C) Experimental regime of CCl4 model in WT and Wisp1 KO mice at indicated timepoints: 3 weeks (oil/WT, n = 3; CCl4/WT, n = 9; oil/KO, n = 5; CCl4/KO, n = 10) and 6 weeks (oil/WT, n = 4; CCl4/WT, n = 10; oil/KO, n = 4; CCl4/KO, n = 11). (D) Representative trichrome staining images of livers after 3- or 6-week CCl4 treatment; scale bars, 500 mm. (E and F) Quantification of fibrosis by relative lesion size (E) and hydroxyproline (F). (G) Representative western blot of type I collagen and cytoskeleton proteins in liver lysates after 6-week CCl4 treatment. GAPDH is a loading control.
Article Snippet: REAGENT or
Techniques: Gene Expression, Staining, Western Blot, Control
Journal: Cell metabolism
Article Title: A WISP1 antibody inhibits MRTF signaling to prevent the progression of established liver fibrosis.
doi: 10.1016/j.cmet.2022.07.009
Figure Lengend Snippet: Figure 4. WISP1 induces cytoskeleton and motility reprogramming via multiple integrins (A) Representative western blots of hWISP1 induced MRTFA and MRTFB nuclear translocation in HSCs in the presence ofArg-Gly-Asp-Ser (RGDS) or Arg-Gly- Glu-Ser (RGES) peptides. YY1 is a loading control for nuclear fractions, and GAPDH is a loading control for whole-cell lysates. (B) hWISP1 induced cytoskeleton gene expression in the presence of RGDS or RGES peptides in HSCs, n = 3 biological replicates. (C) hWISP1 induced HSC migration in the presence of RGDS or RGES peptides, n = 4 biological replicates. (D–F) hWISP1 induced migration (D), MRTFA and MRTFB nuclear translocation (E), and cytoskeleton gene expression (F) of HSCs transfected with siRNAs tar- geting integrins as indicated, n = 4 (D) or 3 (F) biological replicates. (G and H) RHOA activation (G) and F-actin formation (H) in HSCs stimulated with hWISP1 in the presence of RGDS or RGES peptides, n = 3 (G) or 4 (H) biological replicates. (I and J) RHOA activation (I) and F-actin formation (J) in HSCs transfected with siRNAs targeting integrins as indicated, n = 3 (I) or 4 (J) biological replicates. Data in (B)–(J) except (E) represent mean ± SEM, and similar results were seen in at least three independent experiments. p value is calculated using: (C, F, I, and J) two-way ANOVA and (B, D, G, and H) one-way ANOVA. See also Figure S9.
Article Snippet: REAGENT or
Techniques: Western Blot, Translocation Assay, Control, Gene Expression, Migration, Transfection, Activation Assay
Journal: Cell metabolism
Article Title: A WISP1 antibody inhibits MRTF signaling to prevent the progression of established liver fibrosis.
doi: 10.1016/j.cmet.2022.07.009
Figure Lengend Snippet: Figure 5. Discovery of a WISP1-blocking antibody with therapeutic benefits (A and B) Biacore sensorgram plots of anti-WISP1 binding to hWISP1 (A) or mWISP1 (B). (C) Dose-dependent inhibitory activity of anti-WISP1 against hWISP1 induced HSC migration, n = 4 biological replicates.
Article Snippet: REAGENT or
Techniques: Blocking Assay, Binding Assay, Activity Assay, Migration
Journal: Cell metabolism
Article Title: A WISP1 antibody inhibits MRTF signaling to prevent the progression of established liver fibrosis.
doi: 10.1016/j.cmet.2022.07.009
Figure Lengend Snippet: Figure 6. Therapeutic benefits of WISP1 blocking antibody in CDA-HFD NASH model (A) Unsupervised hierarchical clustering analysis of 25-gene NASH fibrosis signature gene expression in livers from mice fed with normal chow and CDA-HFD diet (8 weeks and 16 weeks). (B) Dosing regime in the preventive (weeks 0–8) and therapeutic (weeks 9–16) CDA-HFD NASH model: n = 10 mice for each group. (C) Representative Sirius red staining images of livers; scale bars, 250 mm. (D and E) Quantification of fibrosis by relative lesion size (D) and newly synthesized hydroxyproline (E). (F) Representative western blots of type I collagen and cytoskeleton proteins in liver lysates from the therapeutic CDA-HFD NASH model. GAPDH is a loading control. (G and H) Representative images (G) and quantification (H) of ACTA2 immunofluorescence in livers; scale bars, 100 mm. Data in (D), (E), and (H) represent mean ± SEM. p value is calculated using one-way ANOVA. See also Figure S11.
Article Snippet: REAGENT or
Techniques: Blocking Assay, Gene Expression, Staining, Synthesized, Western Blot, Control