title: Expression and function of osteopontin in vascular adventitial fibroblasts and pathological vascular remodeling.
abstract: Osteopontin is known to play important roles in various diseases including vascular disorders. However, little is known about its expression and function in vascular adventitial fibroblasts. Adventitial fibroblasts have been shown to play a key role in pathological vascular remodeling associating with various vascular disorders. In this study, we measured activation of Osteopontin and its biological functions in cultured adventitial fibroblasts and injured rat carotid injury arteries induced by balloon angioplasty. Our results showed that angiotensin II and aldosterone increased Osteopontin expression in adventitial fibroblasts in a time- and concentration-dependent manner. MAPKs and AP-1 pathways were involved in Osteopontin upregulation. In addition, Adventitial fibroblast migration stimulated by Angiotensin II and aldosterone required OPN expression. Perivascular delivery of antisense oligonucleotide for Osteopontin suppressed neointimal formation post-injury. We concluded that upregulation of Osteopontin expression in adventitial fibroblasts might be important in the pathogenesis of vascular remodeling after arterial injury.
authors.affiliation: Laboratory of Vascular Biology, Institute of Health Science, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Guo-xiang
authors.initials: GX
authors.lastname: Fu
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Li
authors.forename: Ding-liang
authors.initials: DL
authors.lastname: Zhu
authors.forename: Ping-jin
authors.initials: PJ
authors.lastname: Gao
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D015153:Blotting, Western; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003238:Connective Tissue / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D020319:Oligodeoxyribonucleotides, Antisense; D018808:Transcription Factor AP-1; D014662:Vasoconstrictor Agents; D053495:Osteopontin; D000804:Angiotensin II; D000450:Aldosterone; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one