Injury-induced osteopontin gene expression in rat arterial smooth muscle cells is dependent on mitogen-activated protein kinases ERK1/ERK2

Previous work shows that osteopontin has a role during matrix reorganizatio n after tissue injury including vascular conditions such as atherosclerosis and restenosis following angioplasty. In vitro, osteopontin promotes activ ities such as adhesion and migration but the mechanisms that regulate the e xpression of this matrix protein remain essentially unknown. This study exa mined if the ERK signaling pathway is involved in injury-induced osteoponti n expression in cultured rat aortic smooth muscle cells. Northern and Weste rn blotting demonstrated a marked activation of osteopontin expression in r esponse to injury. Treating the cells with PD98059, a specific MEK1 inhibit or, prior to injury, blocked this upregulation. MEK1 phosphorylates ERK1/ E RK2, which belong to the family of mitogen-activated protein kinases. We co nclude that ERK1/ERK2 are involved in the regulation of osteopontin express ion in cultured vascular smooth muscle cells. (C) 2001 Elsevier Science.