Expression and function of osteopontin in vascular adventitial fibroblasts and pathological vascular remodeling.

Expression and function of osteopontin in vascular adventitial fibroblasts and pathological vascular remodeling.
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骨桥蛋白在血管外膜成纤维细胞和病理血管重塑中的表达和功能。

DOI:
10.1371/journal.pone.0023558
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Gao PJ
Gao PJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jin X;Fu GX;Li XD;Zhu DL;Gao PJ

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已知骨桥蛋白在包括血管疾病在内的各种疾病中发挥重要作用。然而,目前对其在血管外膜成纤维细胞中的表达和功能知之甚少。外膜成纤维细胞在与各种血管疾病相关的病理性血管重塑中起关键作用。在本研究中,我们检测了培养的外膜成纤维细胞和球囊血管成形术损伤的大鼠颈动脉中骨桥蛋白的激活及其生物学功能。我们的结果表明,血管紧张素II和醛固酮以时间和浓度依赖的方式增加外膜成纤维细胞骨桥蛋白的表达。MAPKs和AP-1通路参与骨桥蛋白的上调。此外,血管紧张素II和醛固酮刺激的外膜成纤维细胞迁移需要OPN的表达。血管周围注射骨桥蛋白反义寡核苷酸可抑制损伤后新生内膜的形成。结论:外膜成纤维细胞骨桥蛋白表达上调可能在动脉损伤后血管重塑的发病机制中起重要作用。
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.
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