The present study investigated whether TGF-β1 promotes fibrotic changes in HK-2 cells through the Activin A and STAT3 signaling pathways in vitro. Bioinformatics analysis of microarray profiles (GSE20247 and GSE23338) and a protein-protein interaction (PPI) analysis were performed to select hub genes. For the in vitro study, HK-2 cells were exposed to TGF-β1. The expression of Activin A and STAT3 was assayed, and the effect of Activin A and STAT3 expression on fibrosis was assessed (Collagen I and Fibronectin). The bioinformatics study revealed TGF-β1 and Activin A as hub genes. The in vitro study showed that Activin A expression was significantly increased after TGF-β1 incubation. Blocking Activin A attenuated TGF-β1-induced fibrosis. In addition, Activin A blockade attenuated TGF-β1-induced STAT3 signaling pathway activation and related fibrosis. More importantly, STAT3 inhibition by S3I-201 alleviated TGF-β1-induced fibrosis. Activin A promoted cellular fibrotic changes through the STAT3 signaling pathway. Attenuating Activin A expression to mediate the STAT3 signaling pathway might be a strategy for potent renal fibrosis treatment.
Keywords: Activin A; Bioinformatics analysis; Renal fibrosis; STAT3; TGF-β.
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