EGF family ligand-dependent phenotypic modulation of smooth muscle cells through EGF receptor

The phenotypic modulation of smooth muscle cells (SMCs) is closely associat ed with the development and progression of various SMC diseases, We investi gated the molecular mechanism of phenotypic modulation triggered by EGF fam ily ligands using a primary culture system of differentiated SMCs. Among fo ur EGF-receptor (EGFR) family members, the EGFR was solely activated by EGF , heparin-binding EGF (HB-EGF), transforming growth factor alpha (TGF alpha ), epiregulin (ER), and betacellulin (BTC), resulting in induction of pheno typic modulation of SMCs, This effect was mediated through the coordinated activation of the extracellular signal-regulated kinase (ERK) and p38 mitog en-activated protein kinase (p38MAPK) pathways. These results suggest that EGF family ligand- and EGFR-triggered signaling pathways are critically inv olved in the phenotypic modulation of SMCs, (C) 2001 Academic Press.