title: BMP-2 suppresses renal interstitial fibrosis by regulating epithelial-mesenchymal transition.
abstract: Dysregulation of epithelial-to-mesenchymal transition (EMT) may contribute to renal fibrogenesis. Our previous study indicated that bone morphogenetic protein-2 (BMP-2) significantly reversed transforming growth factor (TGF)-β1-induced renal interstitial fibrosis. In this study, we examined the underlying mechanism and elucidate the regulation of EMT process under BMP-2 treatment. Cultured renal interstitial fibroblast (NRK-49F) was treated with TGF-β1 (10 ng/ml) with or without BMP-2 (10-250 ng/ml) for 24 h. The expression of α-smooth muscle actin (α-SMA), E-cadherin, fibronectin, or Snail transcriptional factors was analyzed by immunofluorescence staining or Western blotting. Cell migration was analyzed by wound-healing assay. NRK-49F treated with TGF-β1 induced significant EMT including upregulatioin of α-SMA, fibronectin, and snail proteins and down-regulation of E-cadherin. Interestingly, co-treatment with BMP-2 dose-dependently reversed TGF-β1-induced cellular fibrosis, cell migration, and above EMT change. The above effect was closely correlated with Snail since BMP-2 dose- and time-course dependently induced a significant decrease in the level of Snail. Moreover, Snail siRNA significantly reversed TGF-β1-induced increases in the level of α-SMA and fibronectin (intracellular and extracellular). We suppose that BMP-2 have the potential to attenuate TGF-β1-induced renal interstitial fibrosis by attenuating Snail expression and reversing EMT process.
authors: Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Taiwan. call0955443221@gmail.com
authors: Yu-Lin
authors: YL
authors: Yang
authors: Hong-Zen
authors: HZ
authors: Ju
authors: Shu-Fen
authors: SF
authors: Liu
authors: Tao-Chen
authors: TC
authors: Lee
authors: Yuan-Wei
authors: YW
authors: Shih
authors: Lea-Yea
authors: LY
authors: Chuang
authors: Jinn-Yuh
authors: JY
authors: Guh
authors: Ya-Ying
authors: YY
authors: Yang
authors: Tung-Nan
authors: TN
authors: Liao
authors: Tsung-Jen
authors: TJ
authors: Hung
authors: Min-Yuan
authors: MY
authors: Hung