Osteopontin enhances migratory ability of cultured aortic adventitial fibroblasts from spontaneously hypertensive rats / 生理学报

ABSTRACT

Migration of adventitial fibroblasts (AF) is involved in the neointimal formation which is one of the common pathological processes in several vascular diseases. The observation of whether the migratory response of AF from hypertensive animal is different from that of controls may provide an explanation of vascular remodeling in hypertension. We examined whether there is any difference between the migratory activity of AF derived from spontaneously hypertensive rat (SHR) and that from their normotensive counterpart Wistar-Kyoto rats (WKY). In addition, the role of osteopontin (OPN) in cell migration was also examined. Primary cultures of aortic adventitial fibroblasts were derived from SHR and age-matched WKY. Migration of fibroblasts was determined with the Transwell method. The mRNA expression level of OPN was measured by a real-time quantitative PCR. When compared with WKY-derived cells, migration of adventitial fibroblasts from SHR exhibited an increased response when stimulated by 10% serum (cell number per field 35.20+/-5.26 vs 22.2+/-3.27, p<0.05). Chemotaxis induced by 10 ng/ml bFGF showed a similar difference (cell number per field 30.23+/-4.54 vs 19.20+/-4.47, p<0.05). We also found that SHR-derived fibroblasts expressed a higher level of OPN mRNA than the cells from WKY (1863.23+/-43.91 vs 326.24+/-68.29, p<0.01). To verify if OPN is associated with the enhanced migratory ability in AF from SHR, we designed the antisense oligonucleotide of OPN. The results showed that the antisense OPN oligonucleotide significantly inhibited AF migration (cell number per field 38.60+/-5.98 vs 26.61+/-3.84, p<0.05), while sense and mismatch OPN oligonucleotide had no effect on cell migration. Therefore, the migration of adventitial fibroblasts appeared to be enhanced in cultures derived from SHR. OPN might be involved in the difference observed.