CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin ß1/focal adhesion kinase pathway
CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin ß1/focal adhesion kinase pathway
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DOI：
10.2152/jmi.58.188
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发表时间：
2011-08-01
影响因子：
0.7
通讯作者：
Sone, Saburo
中科院分区：
文献类型：
--
作者：
Batmunkh, Rentsenkhand;Nishioka, Yasuhiko;Sone, Saburo
特发性肺纤维化是一种进行性和致死性肺疾病，其特征是成纤维细胞增殖和细胞外基质沉积增加。CCN6/WISP-3是基质细胞蛋白CCN家族的一员，该家族由6个成员组成，参与许多重要的生物学功能。然而，CCN6蛋白对肺成纤维细胞的调控尚未完全阐明。在这里，我们证明了CCN6通过结合整合素ss1诱导肺成纤维细胞增殖，导致FAKY397磷酸化。此外，CCN6表现出微弱但显著的刺激纤维连接蛋白表达的能力。CCN6在博来霉素处理小鼠肺组织中高表达。我们的研究结果表明，CCN6主要通过刺激肺成纤维细胞的生长在肺的纤维形成中发挥作用，是治疗肺纤维化的潜在靶点。
Idiopathic pulmonary fibrosis is a progressive and lethal disease of the lung that is characterized by the proliferation of fibroblasts and increased deposition of the extracellular matrix. The CCN6/WISP-3 is a member of the CCN family of matricellular proteins, which consists of six members that are involved in many vital biological functions. However, the regulation of lung fibroblasts mediated by CCN6 protein has not been fully elucidated. Here, we demonstrated that CCN6 induced the proliferation of lung fibroblasts by binding to integrin ss 1, leading to the phosphorylation of FAKY397. Furthermore, CCN6 showed a weak, but significant, ability to stimulate the expression of fibronectin. CCN6 was highly expressed in the lung tissues of mice treated with bleomycin. Our results suggest that CCN6 plays a role in the fibrogenesis of the lungs mainly by stimulating the growth of lung fibroblasts and is a potential target for the treatment of pulmonary fibrosis.