The GSK-3/beta-catenin-signalling axis in smooth muscle and its relationship with remodelling.
beta-Catenin is a plasma membrane-associated protein that plays a dual role in cellular signalling by stabilizing cadherin mediated cell-cell contact and by regulating TCF-/LEF-mediated gene transcription. Traditionally, the role of beta-catenin in health and disease has mainly been studied in the context of development and uncontrolled cell growth in diseases such as cancer. Recent findings indicate, however, that beta-catenin also plays a significant role in fibro-proliferative diseases of several organ systems and that beta-catenin regulates mitogenic responses of smooth muscle cells. As several diseases of the internal organs are characterized by structural and phenotypic abnormalities of smooth muscle, including increased fibro-proliferative responses, these findings implicate that beta-catenin could play a broad pathophysiological role. This article will review this potential novel role for beta-catenin and associated intracellular signalling in smooth muscle and discuss the hypothesis that it plays a central role in smooth muscle remodelling.
Gosens
Reinoud
R
Department of Molecular Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713, AV, Groningen, The Netherlands. r.gosens@rug.nl
Meurs
Herman
H
Schmidt
Martina
M
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation; D005355:Fibrosis; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D006984:Hypertrophy; D009130:Muscle, Smooth / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
D015820:Cadherins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3