PAK4 enhances TGF-β1-induced epithelial-mesenchymal transition through activating β-catenin signaling pathway in renal tubular epithelial cells.

Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells contributes to development and progression of renal interstitial fibrosis in CKD. p21-activated kinase 4 (PAK4) is a member of serine/threonine protein kinases but the role of PAK4 in renal fibrosis remains unknown. In this study, we investigated the effects of PAK4 on transforming growth factor-β1 (TGF-β1)-treated human renal tubular epithelial cells (HK-2 cells) and aimed to elucidate probable mechanisms for its fibrogenic effects. Our results revealed that PAK4 was highly expressed in TGF-β1-treated HK-2 cells. Overexpressing PAK4 could further decrease TGF-β1-induced E-cadherin expression and increase TGF-β1-induced fibronectin and vimentin expression in HK-2 cells. In addition, overexpressing PAK4 could promote the translocation of β-catenin from cell membranes into the nucleus in TGF-β1-treated HK-2 cells. These results indicate that PAK4 could enhance TGF-β1-induced EMT in renal tubular epithelial cells. Our findings indicate that PAK4 may promote renal interstitial fibrosis by activating β-catenin signaling pathway. Thus, we suggest that PAK4 might be a potential therapeutic target for ameliorating renal interstitial fibrosis. IJCEP