Fig. 8.

Validation of the role of Wnt5a in regulation of EMT and β-catenin signaling. A–H ARPE-19 cells expressing control shRNA, Wnt5a shRNA-1 or -2 were treated with TGFβ1 (10 ng/mL) for 48 h. A–D qRT-PCR and/or E–H Western blot was employed to examine the mRNA and protein expressions of Wnt5a, fibronectin, α-SMA, collagen I and active β-catenin. I Schematic diagram illustrating the positive feedback loop of Wnt5a/β-catenin involved in the process of EMT of RPE cells and subretinal fibrosis secondary to nAMD. The TGFβ1-induced upregulation of the non-canonical Wnt ligand Wnt5a and activation of canonical β-catenin signaling, forming a reciprocal activation, potentially amplifying disease signals and contributing to EMT and subretinal fibrosis. Line arrows indicate activation, whereas connector lines imply inhibition. I was created with https://www.biorender.com/. Dvl, Dishevelled; EMT, epithelial–mesenchymal transition; LEF, lymphoid enhancer-binding factor; ROR1, receptor tyrosine kinase-like orphan receptor 1; TCF, T-cell factor; TGFβ1, transforming growth factor beta 1