The GSK-3/β-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.