BMP-7 counteracts TGF-β1–induced epithelial-to-mesenchymal transition and reverses chronic renal injury

M Zeisberg, J Hanai, H Sugimoto, T Mammoto… - Nature medicine, 2003 - nature.com
M Zeisberg, J Hanai, H Sugimoto, T Mammoto, D Charytan, F Strutz, R Kalluri
Nature medicine, 2003nature.com
Abstract Bone morphogenic protein (BMP)-7 is a 35-kDa homodimeric protein and a
member of the transforming growth factor (TGF)-β superfamily. BMP-7 expression is highest
in the kidney, and its genetic deletion in mice leads to severe impairment of eye, skeletal
and kidney development. Here we report that BMP-7 reverses TGF-β1–induced epithelial-to-
mesenchymal transition (EMT) by reinduction of E-cadherin, a key epithelial cell adhesion
molecule. Additionally, we provide molecular evidence for Smad-dependent reversal of TGF …
Abstract
Bone morphogenic protein (BMP)-7 is a 35-kDa homodimeric protein and a member of the transforming growth factor (TGF)-β superfamily. BMP-7 expression is highest in the kidney, and its genetic deletion in mice leads to severe impairment of eye, skeletal and kidney development. Here we report that BMP-7 reverses TGF-β1–induced epithelial-to-mesenchymal transition (EMT) by reinduction of E-cadherin, a key epithelial cell adhesion molecule. Additionally, we provide molecular evidence for Smad-dependent reversal of TGF-β1–induced EMT by BMP-7 in renal tubular epithelial cells and mammary ductal epithelial cells. In the kidney, EMT-induced accumulation of myofibroblasts and subsequent tubular atrophy are considered key determinants of renal fibrosis during chronic renal injury. We therefore tested the potential of BMP-7 to reverse TGF-β1–induced de novo EMT in a mouse model of chronic renal injury. Our results show that systemic administration of recombinant human BMP-7 leads to repair of severely damaged renal tubular epithelial cells, in association with reversal of chronic renal injury. Collectively, these results provide evidence of cross talk between BMP-7 and TGF-β1 in the regulation of EMT in health and disease.
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