IMR Press / FBL / Volume 18 / Issue 4 / DOI: 10.2741/4189

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

BMP-7 counteracting TGF-beta1 activities in organ fibrosis

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1 Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Germany
Academic Editor:Steven Dooley
Front. Biosci. (Landmark Ed) 2013, 18(4), 1407–1434; https://doi.org/10.2741/4189
Published: 1 June 2013
(This article belongs to the Special Issue TGF-beta in fibroproliferative diseases)
Abstract

Chronic organ injuries are accompanied by a dysregulated scarring process called "Fibrosis" that is characterized by hyperactivity of TGF-beta resulting in an imbalance of extracellular matrix homeostasis and accumulation of fibrosis-associated proteins. These changes are due to a specialized matrix-expressing cell type, i.e. the myofibroblast, which is derived from independent cellular sources. Beside resident quiescent fibroblasts that become activated, circulating bone-marrow-derived fibrocytes are attracted by the injured organ. Additionally, epithelial cells transit into mesenchymal cells in a process termed epithelial-to-mesenchymal transition. Furthermore, mesothelial cells leave their peripheral location and acquire a fibrogenic phenotype via mesothelial-to-mesenchymal transition. Numerous independent studies have consistently demonstrated that BMP-7 interferes with TGF-beta signaling and a diverse set of matricellular proteins (e.g. CCN proteins), Endoglin, Betaglycan, BAMBI and the members of the repulsive guidance molecule family that modulate cellular proliferation, migration, adhesion and extracellular matrix production. This protein network might therefore depict novel targets for treatment of fibrotic lesions. We here summarize recent knowledge of BMP-7 function and discuss attempts to use this cytokine as a drug to reverse TGF-beta-induced fibrogenesis.

Keywords
Bone morphogenetic protein
transforming growth factor-beta
CCN proteins
intracellular signaling
signaling modulators
Smad proteins
epithelial-tomesenchymal transition
mesothelial-mesenchymal transition
fibrosis
therapy
Review
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