BMP-7 as antagonist of organ fibrosis.
Fibrosis is a scarring process that is a common feature of chronic organ injury. It is characterized by elevated activity of transforming growth factor-beta resulting in increased and altered deposition of extracellular matrix and other fibrosis-associated proteins. Recent work has demonstrated that bone morphogenetic protein-7 blocks transforming growth factor-beta signaling. Moreover, member of the CCN family, Endoglin, Sclerostin, Sclerostin domain-containing proteins, Gremlin, Noggin, Chordin, and Kielin/Chordin-like protein influence the biological activity of both cytokines. As a consequence, they modulate cellular proliferation, migration, adhesion and extracellular matrix production. This tight protein network consisting of transforming growth factor-betas, bone morphogenetic proteins and various binding partners includes potential novel molecular targets and biomarkers useful for prognostication, disease monitoring and therapy. We here summarize recent advances in understanding bone morphogenetic protein-7 function and signaling and the current attempts to use this critical modulator as a pharmacological device to reverse transforming growth factor-beta-induced fibrogenesis.
Weiskirchen
Ralf
R
Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Germany. rweiskirchen@ukaachen.de
Meurer
Steffen K
SK
Gressner
Olav A
OA
Herrmann
Jens
J
Borkham-Kamphorst
Erawan
E
Gressner
Axel M
AM
D000595:Amino Acid Sequence; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D052004:Bone Morphogenetic Protein Receptors / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D005355:Fibrosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D052004:Bone Morphogenetic Protein Receptors