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: Yu-Lin Yang, Hong-Zen Ju, Shu-Fen Liu, Tao-Chen Lee, Yuan-Wei Shih, Lea-Yea Chuang, Jinn-Yuh Guh, Ya-Ying Yang, Tung-Nan Liao, Tsung-Jen Hung, Min-Yuan Hung
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 112 Issue 9 Pg. 2558-65 (Sep 2011) ISSN: 1097-4644 [Electronic] United States
• PMID: 21590708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• Actins
• Antigens, Differentiation
• Bmp2 protein, rat
• Bone Morphogenetic Protein 2
• Cadherins
• Fibronectins
• Snai2 protein, rat
• Snail Family Transcription Factors
• Transcription Factors
• Transforming Growth Factor beta1

Topics

• Actins (metabolism)
• Animals
• Antigens, Differentiation (metabolism)
• Bone Morphogenetic Protein 2 (pharmacology, physiology)
• Cadherins (metabolism)
• Cell Line
• Cell Movement
• Epithelial-Mesenchymal Transition
• Fibroblasts (metabolism, pathology)
• Fibronectins (metabolism)
• Fibrosis
• Kidney (metabolism, pathology)
• RNA Interference
• Rats
• Snail Family Transcription Factors
• Transcription Factors (genetics, metabolism)
• Transforming Growth Factor beta1 (pharmacology, physiology)