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BMP‐2 suppresses renal interstitial fibrosis by regulating epithelial–mesenchymal transition
Author(s) -
Yang YuLin,
Ju HongZen,
Liu ShuFen,
Lee TaoChen,
Shih YuanWei,
Chuang LeaYea,
Guh JinnYuh,
Yang YaYing,
Liao TungNan,
Hung TsungJen,
Hung MinYuan
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23180
Subject(s) - fibronectin , epithelial–mesenchymal transition , snail , transforming growth factor , cell migration , smad , chemistry , fibrosis , wound healing , fibroblast , blot , cancer research , cell , microbiology and biotechnology , biology , medicine , immunology , transition (genetics) , biochemistry , ecology , gene , in vitro
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. J. Cell. Biochem. 112: 2558–2565, 2011. © 2011 Wiley‐Liss, Inc.