Faculty Collaboration Database

BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 2003 Jul;9(7):964-8

Date

06/17/2003

Pubmed ID

12808448

DOI

10.1038/nm888

Scopus ID

2-s2.0-0038717407 (requires institutional sign-in at Scopus site)   1211 Citations

Abstract

Bone morphogenic protein (BMP)-7 is a 35-kDa homodimeric protein and a member of the transforming growth factor (TGF)-beta 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-beta1-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-beta1-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-beta1-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-beta1 in the regulation of EMT in health and disease.

Author List

Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R

Author

Tadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Activin Receptors, Type I
Animals
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins
Cadherins
Cell Differentiation
Cells, Cultured
Chronic Disease
DNA-Binding Proteins
Epithelial Cells
Kidney Tubules
Mesoderm
Mice
Mice, Inbred Strains
Nephritis
Phosphoproteins
Receptors, Transforming Growth Factor beta
Recombinant Proteins
Signal Transduction
Smad3 Protein
Smad5 Protein
Trans-Activators
Transfection
Transforming Growth Factor beta
Transforming Growth Factor beta1