The role of miR-497-5p in myofibroblast differentiation of LR-MSCs and pulmonary fibrogenesis.
The role of miR-497-5p in myofibroblast differentiation of LR-MSCs and pulmonary fibrogenesis.
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miR-497-5p在LR-MSCs肌成纤维细胞分化和肺纤维化中的作用
DOI：
10.1038/srep40958
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发表时间：
2017-01-18
影响因子：
4.6
通讯作者：
Han X
中科院分区：
文献类型：
--
作者：
Chen X;Shi C;Wang C;Liu W;Chu Y;Xiang Z;Hu K;Dong P;Han X
特发性肺纤维化（IPF）是一种慢性、进行性和致死性纤维化肺病，其特征在于干细胞分化、上皮细胞表型和成纤维细胞增殖的深刻变化。在我们的研究中，我们发现miR-497- 5 p在肺驻留间充质干细胞（LR-MSC）的肌成纤维细胞分化期间和肺纤维化模型的肺组织中均显著上调。此外，荧光素酶和Western blot分析表明，具有kazal基序的富含半胱氨酸的逆转诱导蛋白（Reck）是miR-497- 5 p的靶基因之一，Reck可抑制基质金属蛋白酶2（Mmp 2）和Mmp 9的表达，而Mmp 9可激活潜在转化生长因子β1（TGF-β1）。为了测试这种miRNA的潜在治疗意义，我们调节miR-497- 5 p在LR-MSCs和相关动物模型中的表达。结果表明，上调miR-497- 5 p可诱导LR-MSCs向肌成纤维细胞分化，促进肺纤维化的发生，而抑制miR-497- 5 p的表达可有效延缓这一过程。总之，我们的工作支持通过抑制miR-497- 5 p表达来控制肺纤维化可能为IPF提供潜在的治疗策略。
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal fibrotic lung disease characterized by profound changes in stem cell differentiation, epithelial cell phenotypes and fibroblast proliferation. In our study, we found that miR-497-5p was significantly upregulated both during myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSCs) and in the lung tissues of a pulmonary fibrosis model. In addition, as determined by luciferase assays and Western blot analysis, reversion-inducing cysteine-rich protein with kazal motifs (Reck) was identified to be one of the target genes of miR-497-5p, and Reck could suppress the expression of matrix metalloproteinase-2 (Mmp2) and Mmp9, which could activate latent transforming growth factor-β1 (TGF-β1). To test the potential therapeutic significance of this miRNA, we modulated the expression of miR-497-5p in LR-MSCs and relevant animal models. The results demonstrated that upregulation of miR-497-5p could induce LR-MSCs to differentiate into myofibroblasts and promote pulmonary fibrogenesis, while inhibition of its expression could effectively retard these processes. In conclusion, our work supports that controlling pulmonary fibrogenesis via inhibition of miR-497-5p expression may provide a potential therapeutic strategy for IPF.