miR-338-3p 通过诱导 PTEN 阻断 TGFβ 诱导的肌成纤维细胞分化。
miR-338-3p blocks TGFβ-induced myofibroblast differentiation through the induction of PTEN.
机构信息
Lung Biology and Disease Program, University of Rochester Medical Center Rochester, Rochester, New York.
Department of Environmental Medicine, University of Rochester Medical Center Rochester, Rochester, New York.
出版信息
Am J Physiol Lung Cell Mol Physiol. 2022 Mar 1;322(3):L385-L400. doi: 10.1152/ajplung.00251.2021. Epub 2022 Jan 5.
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease. The pathogenesis of IPF is not completely understood. However, numerous genes are associated with the development and progression of pulmonary fibrosis, indicating there is a significant genetic component to the pathogenesis of IPF. Epigenetic influences on the development of human disease, including pulmonary fibrosis, remain to be fully elucidated. In this paper, we identify miR-338-3p as a microRNA severely downregulated in the lungs of patients with pulmonary fibrosis and in experimental models of pulmonary fibrosis. Treatment of primary human lung fibroblasts with miR-338-3p inhibits myofibroblast differentiation and matrix protein production. Published and proposed targets of miR-338-3p such as TGFβ receptor 1, MEK/ERK 1/2, Cdk4, and Cyclin D are also not responsible for the regulation of pulmonary fibroblast behavior by miR-338-3p. miR-338-3p inhibits myofibroblast differentiation by preventing TGFβ-mediated downregulation of phosphatase and tensin homolog (PTEN), a known antifibrotic mediator.
特发性肺纤维化（IPF）是一种慢性间质性肺疾病。IPF 的发病机制尚不完全清楚。然而，许多基因与肺纤维化的发生和进展有关，这表明 IPF 的发病机制存在显著的遗传成分。表观遗传对人类疾病（包括肺纤维化）的影响仍有待充分阐明。在本文中，我们确定 miR-338-3p 是一种在肺纤维化患者的肺部和肺纤维化实验模型中严重下调的 microRNA。用 miR-338-3p 处理原代人肺成纤维细胞可抑制肌成纤维细胞分化和基质蛋白产生。miR-338-3p 的已发表和拟议靶标，如 TGFβ 受体 1、MEK/ERK 1/2、Cdk4 和 Cyclin D，也不是 miR-338-3p 调节肺成纤维细胞行为的原因。miR-338-3p 通过阻止 TGFβ 介导的磷酸酶和张力蛋白同源物（PTEN）下调来抑制肌成纤维细胞分化，PTEN 是一种已知的抗纤维化介质。
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