Transforming growth factor-β increases vascular smooth muscle cell proliferation through the Smad3 and extracellular signal-regulated kinase mitogen-activated protein kinases pathways

Restenosis continues to be the most significant limitation to the long-term success of surgical therapies for atherosclerotic-associated diseases. Although transforming growth factor-β (TGF-β) has been implicated in the pathogenesis of restenosis, anti-TGF therapies could lead to untoward cell growth because it is a known growth inhibitor in a number of cell types. This led to the investigation of downstream mediators of TGF-β, Smad3, and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPK), as more selective targets to repress smooth muscle cell proliferation. This study demonstrates that TGF-β, through its primary signaling pathway Smad3, directly activates the ERK MAPK pathway to increase smooth muscle cell proliferation.