Plant miRNA osa-miR172d-5p suppressed lung fibrosis by targeting Tab1.
Plant miRNA osa-miR172d-5p suppressed lung fibrosis by targeting Tab1.
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DOI：
10.1038/s41598-023-29188-6
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发表时间：
2023-02-06
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
肺纤维化，包括特发性肺纤维化，是一种伴随呼吸系统不可逆功能障碍的难治性疾病。其发病机制涉及转化生长因子β（TGFβ）诱导成纤维细胞细胞外基质的过量产生；然而，已经制定了有限的对策。在这项研究中，我们确定了 osa-miR172d-5p（一种植物来源的 microRNA (miR)）作为一种有效的抗纤维化 miR。计算机分析和基于人肺成纤维细胞的体外测定表明，osa-miR172d-5p 抑制 TGF-β 激活激酶 1 (MAP3K7) 结合蛋白 1 (Tab1) 的基因表达。它还抑制人肺成纤维细胞中 TGFβ 诱导的纤维化基因表达。为了评估 osa-miR172d-5p 的抗纤维化作用，我们建立了博来霉素诱导的肺纤维化模型，以证明 osa-miR172d-5p 可改善肺纤维化。此外，它还抑制博莱霉素治疗小鼠肺组织中 Tab1 的表达。总之，osa-miR172d-5p 可能是治疗肺纤维化（包括特发性肺纤维化）的有效候选药物。
Lung fibrosis, including idiopathic pulmonary fibrosis, is an intractable disease accompanied by an irreversible dysfunction in the respiratory system. Its pathogenesis involves the transforming growth factorβ (TGFβ)-induced overproduction of the extracellular matrix from fibroblasts; however, limited countermeasures have been established. In this study, we identified osa-miR172d-5p, a plant-derived microRNA (miR), as a potent anti-fibrotic miR. In silico analysis followed by an in vitro assay based on human lung fibroblasts demonstrated that osa-miR172d-5p suppressed the gene expression of TGF-β activated kinase 1 (MAP3K7) binding protein 1 (Tab1). It also suppressed the TGFβ-induced fibrotic gene expression in human lung fibroblasts. To assess the anti-fibrotic effect of osa-miR172d-5p, we established bleomycin-induced lung fibrosis models to demonstrate that osa-miR172d-5p ameliorated lung fibrosis. Moreover, it suppressed Tab1 expression in the lung tissues of bleomycin-treated mice. In conclusion, osa-miR172d-5p could be a potent candidate for the treatment of lung fibrosis, including idiopathic pulmonary fibrosis.
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影响因子：
5.6
作者：
Kendall RT;Feghali-Bostwick CA
通讯作者：
Feghali-Bostwick CA
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通讯作者：
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通讯作者：
Romero, Yair