College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Toxicol Appl Pharmacol. 2018 Nov 1;358:35-42. doi: 10.1016/j.taap.2018.09.007. Epub 2018 Sep 7.
Fibroblast-to-myofibroblast differentiation is a highly important pathological characteristic of pulmonary fibrosis. In this study, we aimed to investigate the effects and mechanisms of baicalein on the differentiation of human lung fibroblasts. Baicalein reduced the levels of α-smooth muscle actin (α-SMA) mRNA and protein expression in TGF-β1-treated human lung fibroblasts. It also decreased the contents of collagen type I and fibronectin in time- and dose-dependent manners, and retarded TGF-β1-stimulated α-SMA filament formation. Baicalein diminished the expression of miR-21, and miR-21 mimics partially antagonized the effects of baicalein. Additionally, Baicalein inhibited the miR-21 transcriptor STAT3 activity but not AP-1 activity. Moreover, the expression of Spry 1 protein, a miR-21 known target, was improved by baicalein treatment, but the level of Smurf2 protein, another miR-21 target, was not interfered. Collectively, these results demonstrated that baicalein can attenuate TGF-β1-induced human lung fibroblast differentiation by inhibiting the miR-21 expression.
成纤维细胞向肌成纤维细胞的分化是肺纤维化的一个重要病理特征。在本研究中，我们旨在探讨白杨素对人肺成纤维细胞分化的影响及作用机制。白杨素可降低 TGF-β1 处理的人肺成纤维细胞中α-平滑肌肌动蛋白（α-SMA）mRNA 和蛋白的表达水平。它还可呈时间和剂量依赖性地降低Ⅰ型胶原和纤维连接蛋白的含量，并抑制 TGF-β1 刺激的α-SMA 丝形成。白杨素降低了 miR-21 的表达，而 miR-21 模拟物部分拮抗了白杨素的作用。此外，白杨素抑制了 miR-21 转录因子 STAT3 的活性，但不影响 AP-1 的活性。此外，白杨素处理可改善 miR-21 已知靶标 Spry 1 蛋白的表达，但不干扰另一个 miR-21 靶标 Smurf2 蛋白的水平。总之，这些结果表明，白杨素通过抑制 miR-21 的表达来减轻 TGF-β1 诱导的人肺成纤维细胞分化。
