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

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.

Authors+Show Affiliations

Center for Matrix Biology, Gastroenterology and Renal Divisions, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12808448

Citation

Zeisberg, Michael, et al. "BMP-7 Counteracts TGF-beta1-induced Epithelial-to-mesenchymal Transition and Reverses Chronic Renal Injury." Nature Medicine, vol. 9, no. 7, 2003, pp. 964-8.
Zeisberg M, Hanai J, Sugimoto H, et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med. 2003;9(7):964-8.
Zeisberg, M., Hanai, J., Sugimoto, H., Mammoto, T., Charytan, D., Strutz, F., & Kalluri, R. (2003). BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nature Medicine, 9(7), 964-8.
Zeisberg M, et al. BMP-7 Counteracts TGF-beta1-induced Epithelial-to-mesenchymal Transition and Reverses Chronic Renal Injury. Nat Med. 2003;9(7):964-8. PubMed PMID: 12808448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. AU - Zeisberg,Michael, AU - Hanai,Jun-ichi, AU - Sugimoto,Hikaru, AU - Mammoto,Tadanori, AU - Charytan,David, AU - Strutz,Frank, AU - Kalluri,Raghu, PY - 2003/01/14/received PY - 2003/05/23/accepted PY - 2003/6/17/pubmed PY - 2003/8/29/medline PY - 2003/6/17/entrez SP - 964 EP - 8 JF - Nature medicine JO - Nat Med VL - 9 IS - 7 N2 - 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. SN - 1078-8956 UR - https://www.unboundmedicine.com/medline/citation/12808448/BMP_7_counteracts_TGF_beta1_induced_epithelial_to_mesenchymal_transition_and_reverses_chronic_renal_injury_ L2 - https://doi.org/10.1038/nm888 DB - PRIME DP - Unbound Medicine ER -