Periostin regulates fibrocyte function to promote myofibroblast differentiation and lung fibrosis.
Periostin regulates fibrocyte function to promote myofibroblast differentiation and lung fibrosis.
复制标题
骨膜素调节纤维细胞功能以促进肌纤维细胞分化和肺纤维化。
DOI：
10.1038/mi.2016.61
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发表时间：
2017-03
影响因子：
8
通讯作者：
Moore BB
中科院分区：
文献类型：
--
作者：
Ashley SL;Wilke CA;Kim KK;Moore BB
纤维细胞是募集到纤维化区域的循环间充质前体细胞(CD45+，Col1+)。纤维细胞分泌促纤维化介质，包括Periostin；Periostin是一种基质蛋白，调节细胞与细胞外基质(ECM)成分的相互作用。在博莱霉素诱导的纤维化中，结构细胞或造血细胞中的Periostin缺乏限制了肺纤维化的发展。为了确定造血源性成纤维细胞是否可能分泌可溶性因子来激活结构肌成纤维细胞分化，用博莱霉素处理的野生型(WT)成纤维细胞或Periostin−/−小鼠分离的成纤维细胞的条件培养液处理WT成纤维细胞。24小时后，我们看到α-平滑肌肌动蛋白在经Periostin−/−纤维细胞条件培养液处理的细胞中表达减少。与Periostin−/−小鼠的纤维细胞相比，WT纤维细胞过继转移对肺纤维化的促进作用更大。对WT和Periostin−/−小鼠分离的纤维细胞和成纤维细胞的体外分析表明，转化生长因子β1或Periostin处理后，间充质激活和β1整合素作为Periostin潜在受体在纤维细胞上共同调节。此外，Periostin处理的纤维细胞结缔组织生长因子(CTGFm RNA)表达增加，而博莱霉素Periostin−/−纤维细胞结缔组织生长因子(CTGFm RNA)和溶质氧化酶(Loxm RNA)的表达较低。这些数据表明，纤维细胞可能通过分泌Periostin和其他促进肌成纤维细胞分化的可溶性因子来增强博莱霉素诱导的纤维化。
Fibrocytes are circulating mesenchymal precursors (CD45+, col 1+) recruited to fibrotic areas. Fibrocytes secrete profibrotic mediators including periostin; a matricellular protein that regulates cellular interactions with extracellular matrix (ECM) components. In bleomycin-induced fibrosis, periostin deficiency in structural or hematopoietic cells limits development of pulmonary fibrosis. To determine if hematopoietic-derived fibrocytes might secrete soluble factors to activate structural myofibroblast differentiation, wild-type (WT) fibroblasts were treated with conditioned medium from fibrocytes isolated from bleomycin-treated WT or periostin−/− mice. After 24 hours we saw less α-smooth muscle actin expression in cells treated with conditioned medium from periostin−/− fibrocytes. Adoptive transfer of WT fibrocytes augmented lung fibrosis to a greater extent than transfer of fibrocytes from periostin−/− mice. In vitro analysis of fibrocytes and fibroblasts isolated from WT and periostin −/− mice treated with TGFβ1 or periostin demonstrated co-regulation of mesenchymal activation and beta 1 integrin as a potential receptor for periostin on fibrocytes. Additionally, connective tissue growth factor (CTGF) mRNA expression was increased in fibrocytes treated with periostin whereas CTGF and lysl oxidase (LOX) mRNA expression was low in bleomycin-treated periostin−/− fibrocytes. These data suggest fibrocytes may augment bleomycin-induced fibrosis via secretion of periostin and other soluble factors that promote myofibroblast differentiation.