Abstract Fibrosis is a phenomenon in which parenchyma is replaced with fibrous tissue. Persistent inflammation accompanied by dysregulation of cytokine production and repeated cycles of inflammation-associated tissue-repair induces fibrosis in various organs including the liver, lung, and kidney. In idiopathic pulmonary fibrosis, production of interleukin (IL)-6 and osteopontin (OPN) are dysregulated. Fibrosis leads to qualitative rather than quantitative changes of fibroblasts at the sites of tissue repair, and this leads to enlargement of fibrotic foci. These fibroblasts are immunohistochemically positive for OPN; however, the effect of overexpressed OPN in fibroblasts is not fully understood yet. In this study, we investigated the effect of OPN on IL-6 secretion and on migration and proliferation of fibroblasts. Lung fibroblasts overexpressing exogenous OPN showed that OPN was linked to the enhancement of cell migration through increased IL-6 secretion via the extracellular signal-regulated kinase (ERK) pathway. These results suggest that OPN may exert its pro-fibrotic functions, such as enhancement of fibroblasts migration by cooperating with chemoattractant IL-6, and may be involved in enlargement of fibrotic foci.

中文翻译：

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骨桥蛋白通过 ERK 通路上调白细胞介素 6 增强肺成纤维细胞的迁移

摘要 纤维化是实质被纤维组织取代的现象。持续的炎症伴随着细胞因子产生的失调和炎症相关组织修复的重复循环，会导致包括肝、肺和肾在内的各种器官的纤维化。在特发性肺纤维化中，白细胞介素 (IL)-6 和骨桥蛋白 (OPN) 的产生失调。纤维化导致组织修复部位的成纤维细胞发生质的变化而不是数量的变化，这导致纤维化病灶的扩大。这些成纤维细胞的 OPN 免疫组化阳性；然而，过表达的 OPN 在成纤维细胞中的作用尚未完全清楚。在这项研究中，我们研究了 OPN 对 IL-6 分泌和成纤维细胞迁移和增殖的影响。过度表达外源性 OPN 的肺成纤维细胞表明，OPN 与通过细胞外信号调节激酶 (ERK) 途径增加 IL-6 分泌而增强细胞迁移有关。这些结果表明 OPN 可能发挥其促纤维化功能，例如通过与化学引诱剂 IL-6 合作增强成纤维细胞迁移，并可能参与纤维化病灶的扩大。