MiR-185 affected the EMT, cell viability, and proliferation via DNMT1/MEG3 pathway in TGF-β1-induced renal fibrosis.

Abstract

Kidney fibrosis is usually the final manifestation of a wide variety of renal diseases. Recent years, research reported that long non-coding RNAs (lncRNAs) played important roles in a variety of human diseases. However, the role and underlying mechanisms of lncRNAs in kidney fibrosis were complicated and largely unclear. In our study, we constructed the cell model of renal fibrosis in HK2 cells using transforming growth factor β1 (TGF-β1) and found that lncRNA maternally expressed gene 3 (MEG3) was downregulated in TGF-β1-induced renal fibrosis. We then found that overexpressed MEG3 inhibited the TGF-β1-induced promotion of epithelial-mesenchymal transition, cell viability, and proliferation. Furthermore, we demonstrated that DNA methyltransferases 1 (DNMT1) regulated the MEG3 expression by altering the CpGs methylation level of MEG3 promoter in TGF-β1-induced renal fibrosis. In addition, we further revealed that miR-185 could regulate the DNMT1 expression and thus, modulate the MEG3 in TGF-β1-induced renal fibrosis. Ultimately, our study illustrated that the modulation of the miR-185/ DNMT1/ MEG3 pathway exerted important roles in TGF-β1-induced renal fibrosis. In summary, our finding displayed a novel regulatory mechanism for TGF-β1-induced renal fibrosis, which provided a new potential therapeutic target for renal fibrosis.