Fig. 2: Identification of β-catenin as the major effector mediating MMP-10 action.
From: Matrix metalloproteinase-10 promotes kidney fibrosis by transactivating β-catenin signaling
A–C Western blotting showed that rhMMP-10 (100 ng/ml) induced fibronectin and α-smooth muscle actin (α-SMA) and repressed E-cadherin in HK-2 cells. Representative Western blotting (A) and quantitative data (B, C) are reported. Data are presented as the mean ± SEM. ***P < 0.001 versus the controls (n = 6). D STRING analysis revealed the protein-protein interaction (PPI) network involving MMP-10 (https://cn.string-db.org/, accessed on 8 August 2023). The interaction between MMP-10 and β-catenin was noticed. E Analysis of the Cancer Dependency Map (https://depmap.org, accessed on 10 August 2023) revealed the correlation between MMP-10 expression and alteration in β-catenin. Linear regression (left) and volcano plot (right) demonstrated a positive correlation between MMP-10 and β-catenin. F, H RhMMP-10 activated β-catenin signaling in vitro, leading to the induction of active β-catenin, PAI-1, and MMP-7 proteins. Data are presented as the mean ± SEM. **P < 0.01, ***P < 0.001 versus the controls (n = 6). I Representative micrographs showed the nuclear translocation of β-catenin after rhMMP-10 treatment for 12 h. White arrows indicate nuclear staining of β-catenin. Scale bar, 50 µm. J, K ICG-001 (10 μM) abolished MMP-10-mediated fibronectin and α-SMA expression. Data are presented as the mean ± SEM. ***P < 0.001 versus the controls (n = 6); †††P < 0.001 versus rhMMP-10 alone (n = 6). L Representative immunofluorescence staining showed that ICG-001 inhibited fibronectin expression and deposition induced by MMP-10. Scale bar, 50 µm. M, N ICG-001 inhibited MMP-10-mediated β-catenin activation and its downstream MMP-7 and PAI-1 induction. Representative Western blotting (M) and quantitative data (N) were presented. Data are presented as the mean ± SEM. **P < 0.01, ***P < 0.001 versus the controls (n = 6); ††P < 0.01, †††P < 0.001 versus rhMMP-10 alone (n = 6). O qRT-PCR analysis showed that rhMMP-10 did not significantly affect the expression of Wnt ligands except Wnt10a. Data are presented as the mean ± SEM. *P < 0.05 versus controls (n = 6).
