Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1523-1529. doi: 10.3892/mmr.2017.6711. Epub 2017 Jun 7.
The myofibroblast has been implicated to be an important pathogenic cell in all fibrotic diseases, through synthesis of excess extracellular matrix. Lung fibroblast migration, proliferation and differentiation into a myofibroblast‑like cell type are regarded as important steps in the formation of lung fibrosis. In the present study, the effect of maresin 1 (MaR 1), a pro‑resolving lipid mediator, on transforming growth factor (TGF)‑β1‑stimulated lung fibroblasts was investigated, and the underlying molecular mechanisms were examined. The results of the present study demonstrated that MaR 1 inhibited TGF‑β1‑induced proliferative and migratory ability, assessed using MTT and scratch wound healing assays. The TGF‑β1‑induced expression of α‑smooth muscle actin (α‑SMA) and collagen type I, the hallmarks of myofibroblast differentiation, was decreased by MaR 1 at the mRNA and protein levels, determined using the reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. Immunofluorescence demonstrated that MaR 1 downregulated the TGF‑β1‑induced expression of α‑SMA. In addition, phosphorylated mothers against decapentaplegic homolog 2/3 (Smad2/3) and extracellular signal‑related kinases (ERK) 1/2 were upregulated in TGF-β1-induced lung fibroblasts, and these effects were attenuated by MaR 1 administration. In conclusion, the results of the present study demonstrated that MaR 1 inhibited the TGF‑β1‑induced proliferation, migration and differentiation of human lung fibroblasts. These observed effects may be mediated in part by decreased phosphorylation of Smad2/3 and ERK1/2 signaling pathways. Therefore, MaR 1 may be a potential therapeutic approach to lung fibrotic diseases.
肌成纤维细胞已被认为是所有纤维化疾病中的一种重要致病细胞，通过合成过量的细胞外基质。肺成纤维细胞的迁移、增殖和分化为肌成纤维细胞样细胞类型被认为是肺纤维化形成的重要步骤。在本研究中，研究了促分解脂质介质maresin 1（MaR 1）对转化生长因子（TGF）-β1 刺激的肺成纤维细胞的影响，并研究了其潜在的分子机制。本研究结果表明，MaR 1 抑制 TGF-β1 诱导的增殖和迁移能力，通过 MTT 和划痕愈合实验进行评估。TGF-β1 诱导的α-平滑肌肌动蛋白（α-SMA）和 I 型胶原的表达，作为肌成纤维细胞分化的标志，通过 MaR 1 在 mRNA 和蛋白水平上降低，通过逆转录-定量聚合酶链反应和蛋白质印迹分析分别进行评估。免疫荧光显示 MaR 1 下调了 TGF-β1 诱导的α-SMA 的表达。此外，TGF-β1 诱导的肺成纤维细胞中磷酸化 mothers against decapentaplegic homolog 2/3（Smad2/3）和细胞外信号调节激酶（ERK）1/2 表达上调，MaR 1 给药可减弱这些作用。综上所述，本研究结果表明，MaR 1 抑制 TGF-β1 诱导的人肺成纤维细胞增殖、迁移和分化。这些观察到的作用可能部分是通过降低 Smad2/3 和 ERK1/2 信号通路的磷酸化来介导的。因此，MaR 1 可能是治疗肺纤维化疾病的一种潜在方法。
