在矽肺中，生长分化因子15（GDF15）通过miR-338/信号转导和转录激活因子1（STAT1）激活人成纤维细胞MRC5细胞。
GDF15 activates human fibroblast MRC5 cells via miR-338/STAT1 in silicosis.
作者信息
Wu Ge-Ting, Tian Qiu-Yan, Xie Bin, Hu Yong-Bin, Deng Zheng-Hao
机构信息
Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Department of Pathology, Hunan Prevention and Treatment Institute for Occupational Diseases, Changsha, 410000, Hunan, China.
出版信息
Clin Exp Med. 2025 Mar 20;25(1):91. doi: 10.1007/s10238-025-01627-w.
Growth differentiation factor 15 (GDF-15) has been implicated in multiple biological functions. However, the role of GDF15 in silicosis remains unclear. In this study, the serum level of GDF-15 was investigated in 46 patients with silicosis by ELISA and results showed it was higher than that of control patients. The effects of exogenous GDF15 on mRNA and miRNA expression profiles of MRC5 cells were analyzed by RNA sequencing. GDF15 activated human embryonic lung fibroblast MRC5 cells with upregulation of col1a and α-SMA. GDF15 reduced miR-338 expression and increased STAT1 expression in MRC5 cells. The results of the luciferase reporter assay and bioinformatics analysis indicated that STAT1 was a direct target of miR-338. miR-338 mimics down-regulated col1a and α-SMA expression induced by GDF15 with STAT1 overexpression, whereas miR-338 inhibitor up-regulated col1a and α-SMA expression induced by GDF15 with STAT1 knockdown. Those results indicated GDF15 activated MRC5 cells through the miR-338/STAT1 pathway and GDF-15 may play an important role in silicosis.
生长分化因子15（GDF-15）参与多种生物学功能。然而，GDF15在矽肺中的作用仍不清楚。在本研究中，采用酶联免疫吸附测定法（ELISA）检测了46例矽肺患者血清中GDF-15水平，结果显示其高于对照患者。通过RNA测序分析了外源性GDF15对MRC5细胞mRNA和miRNA表达谱的影响。GDF15激活人胚肺成纤维细胞MRC5，使col1a和α-SMA表达上调。GDF15降低MRC5细胞中miR-338表达并增加STAT1表达。荧光素酶报告基因检测和生物信息学分析结果表明，STAT1是miR-338的直接靶点。miR-338模拟物通过过表达STAT1下调GDF15诱导的col1a和α-SMA表达，而miR-338抑制剂通过敲低STAT1上调GDF15诱导的col1a和α-SMA表达。这些结果表明，GDF15通过miR-338/STAT1途径激活MRC5细胞，GDF-15可能在矽肺中起重要作用。
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