Department of Interdisciplinary, Program in Biomedical Science Major, Graduate School, Soonchunhyang University, Asan 31538, Republic of Korea.
Department of Microbiology and BK21 Four Project, College of Medicine, Soonchunhyang University, Cheonan 31538, Republic of Korea.
Int J Mol Sci. 2023 Jun 15;24(12):10182. doi: 10.3390/ijms241210182.
Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that erythrocyte membrane protein band 4.1-like 3 () increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of in IPF by comparing the EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of epithelial-mesenchymal transition (EMT) in an epithelial cell line (A549) and fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5) by overexpressing and silencing . EPB41L3 mRNA and protein levels, as measured using RT-PCR, real-time PCR, and Western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-β-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti- transfection suppressed the mRNA and protein expression of and Treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of . Overexpression of in MRC5 cells using lenti- transfection suppressed the mRNA and protein expression of and Finally, treatment with siRNA upregulated the mRNA and protein expression of and In conclusion, these data strongly support an inhibitory effect of on the process of fibrosis and suggest the therapeutic potential of EPB41L3 as an anti-fibrotic mediator.
已鉴定出涉及特发性肺纤维化 (IPF) 发生和预后的新型遗传和表观遗传因素。我们之前观察到，IPF 患者的肺成纤维细胞中红细胞膜蛋白 4.1 样 3 () 增加。因此，我们通过比较 IPF 患者和对照组的肺成纤维细胞中 EPB41L3 mRNA 和蛋白表达，研究了在 IPF 中的作用。我们还通过过表达和沉默研究了上皮细胞系 (A549) 中的上皮-间充质转化 (EMT) 和成纤维细胞向肌成纤维细胞转化 (FMT) 的调节在成纤维细胞系 (MRC5) 中。使用 RT-PCR、实时 PCR 和 Western blot 测量 EPB41L3 mRNA 和蛋白水平，从 14 名 IPF 患者中分离的成纤维细胞中明显高于从 10 名对照中分离的成纤维细胞。在转化生长因子-β诱导的 EMT 和 FMT 期间，EPB41L3 的 mRNA 和蛋白表达上调。用 lenti-转染过表达 A549 细胞中的 EPB41L3 抑制和的 mRNA 和蛋白表达。用 EPB41L3 siRNA 处理上调的 mRNA 和蛋白表达。用 lenti-转染过表达 MRC5 细胞中的 EPB41L3 抑制和的 mRNA 和蛋白表达。最后，用 siRNA 处理上调和的 mRNA 和蛋白表达。总之，这些数据强烈支持对纤维化过程的抑制作用，并表明 EPB41L3 作为抗纤维化介质的治疗潜力。
