Overexpression of BMP‑7 reverses TGF‑β1‑induced epithelial‑mesenchymal transition by attenuating the Wnt3/β‑catenin and TGF-β1/Smad2/3 signaling pathways in HK‑2 cells.

Tubular epithelial cells undergoing epithelial-mesenchymal transition (EMT) is a crucial event in the progression of renal interstitial fibrosis (RIF). Bone morphogenetic protein-7 (BMP-7) has been reported to exhibit anti-fibrotic functions in various renal diseases. However, the function of BMP-7 in regulating EMT and the progression of RIF remains largely unknown. The aim of the present study was to examine the potential effect of BMP-7 on transforming growth factor beta 1 (TGF-beta 1)-induced EMT and the underlying mechanisms by which BMP-7 exerted its effects. Human renal proximal tubular epithelial cells (HK-2) were treated with TGF-beta 1 for various time periods and at various concentrations and lentiviral vectors were used to overexpress BMP-7. Cell Counting Kit-8 and Transwell assays were used to evaluate the viability and migration of HK-2 cells in vitro. EMT was estimated by assessing the changes in cell morphology and the expression of EMT markers. In addition, the activation of the Wnt3/beta-catenin and TGF-beta 1/Smad2/3 signaling pathways were analyzed using western blotting. TGF-beta 1 induced EMT in a time- and dose-dependent manner in HK-2 cells. Treatment with TGF-beta 1 induced morphological changes, decreased cell viability and the expression of E-cadherin, increased cell migration and the expression of alpha-smooth muscle actin, fibroblast-specific protein 1, collagen I and vimentin, and activated the Wnt3/beta-catenin and TGF-beta 1/Smad2/3 signaling pathways in HK-2 cells. However, BMP-7 overexpression notably reversed all these effects. These results suggest that BMP-7 effectively suppresses TGF-beta 1-induced EMT through the inhibition of the Wnt3/beta-catenin and TGF-beta 1/Smad2/3 signaling pathways, highlighting a potential novel anti-RIF strategy.