Osteopontin overexpression is associated with arterial smooth muscle cell proliferation in vitro.

Abstract

To isolate the genes involved in the cell cycle G1 phase progression of arterial smooth muscle cells (SMCs), a cDNA clone (M11) was previously selected by differential hybridization screening of a mid-G1 serum-stimulated SMC cDNA library. The delay of induction after mitogenic stimulation, time of expression, and need for new protein synthesis for full expression made it possible to classify this gene in the "delayed early" gene group. Determination of the partial M11 cDNA sequence showed full homology with the osteopontin gene (secreted phosphoprotein 1, 2ar), an Arg-Gly-Asp-containing extracellular matrix protein. Osteopontin mRNA was also detected in the aorta at levels as high as in the kidney but lower than in bone, two tissues in which it has been previously detected. In vitro analysis of osteopontin expression in serum-stimulated quiescent SMCs and asynchronously cycling SMCs demonstrated that osteopontin overexpression was associated with SMC proliferation. In view of our results, the high osteopontin expression observed by others in the injured carotid artery could be explained by the involvement of SMCs in the proliferative process. Taken together, these results suggest that osteopontin may play an important role in pathological processes that are associated with arterial SMC proliferation, such as atherosclerosis or restenosis.

Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB

“…6C). A closer interpretation of the RT-qPCR data revealed a high basal expression of OPN in the presence of the DMSO vehicle, which has been observed previously in smooth muscle cells (15). Inhibition of p38 resulted in a trend toward reducing the level of ANG II induction of mRNA for all gene targets.…”

“…The confirmed extent of induction of OPN mRNA levels in response to hypertensive disease was particularly intriguing due to the previous implications that OPN regulates VSMC proliferation and migration and is overexpressed during postangioplasty restenosis (15,35,50). In addition, OPN is a matricellular gene that is known to be transcriptionally regulated by ANG II and ERK signaling (7).…”

“…OPN is a marker of proliferation in rat VSMCs, and its expression in cultured VSMCs correlates with the downregulation of contractile proteins, suggesting a switch from the contractile to the proliferative phenotype (15,17,50,56). OPN plays a role in coronary artery postangioplasty restenosis through its chemotactic properties, where it mediates smooth muscle cell extracellular matrix invasion of the intimal layer (35).…”

“…OPN plays a role in coronary artery postangioplasty restenosis through its chemotactic properties, where it mediates smooth muscle cell extracellular matrix invasion of the intimal layer (35). Moreover, OPN has been referred to as a "delayed early gene" because of its role in cell proliferation following mitogenic stimulation in arterial smooth muscle cells (15).…”

Molecular atherectomy for restenosis

“…In vitro, more than a dozen factors in plasma, platelets, endothelial cells, SMCs, and macrophages can each stimulate the proliferation of SMCs (Willerson et al 1991, Ross 1993, Casscells 1991a, and new factors are reported every few months (Gressens et al 1993, Gadeau et al 1993, Grove et al 1993, Shing et al 1993. In many cases, these factors also upregulate other growth factors and their receptors (Hu et al 1992, Nicholson and Hajjar 1992, Hajjar and Pomerantz 1992, Schollmann et al 1992, Stiko-Rahm et al 1992, Itoh et al 1993.…”