GDF15 activates human fibroblast MRC5 cells via miR-338/STAT1 in silicosis

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.