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

Song,Yan; Lv,Shasha; Wang,Fang; Liu,Xiaoli; Cheng,Jing; Liu,Shanshan; Wang,Xiaoying; Chen,Wei; Guan,Guangju; Liu,Gang; Peng,Changliang

doi:10.3892/mmr.2019.10875

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

Authors:
- Yan Song
- Shasha Lv
- Fang Wang
- Xiaoli Liu
- Jing Cheng
- Shanshan Liu
- Xiaoying Wang
- Wei Chen
- Guangju Guan
- Gang Liu
- Changliang Peng
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Affiliations: Department of Nephrology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Institute of Medical Sciences, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Hematology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Pathology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China, Department of Orthopedics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
Published online on: December 10, 2019 https://doi.org/10.3892/mmr.2019.10875
Pages: 833-841
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 β1 (TGF‑β1)‑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‑β1 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/β‑catenin and TGF‑β1/Smad2/3 signaling pathways were analyzed using western blotting. TGF‑β1 induced EMT in a time‑ and dose‑dependent manner in HK‑2 cells. Treatment with TGF‑β1 induced morphological changes, decreased cell viability and the expression of E‑cadherin, increased cell migration and the expression of α‑smooth muscle actin, fibroblast‑specific protein 1, collagen I and vimentin, and activated the Wnt3/β‑catenin and TGF‑β1/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‑β1‑induced EMT through the inhibition of the Wnt3/β‑catenin and TGF‑β1/Smad2/3 signaling pathways, highlighting a potential novel anti‑RIF strategy.

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