Mechanism of DNASE1L3 delaying renal fibrosis by inhibiting PI3K-AKT signaling pathway

Objective To investigate the role and mechanism of deoxyribonuclease 1L3 (DNASE1L3) in renal fibrosis. Methods The renal fibrosis model in vivo was established by unilateral ureteral obstruction in mice. The mRNA and protein expression levels of DNASE1L3 in the kidney were detected by RT-qPCR and WB. TGF-β was used to induce HK-2 cells to construct in vitro fibrosis model, and WB was used to detect the protein expression level of DNASE1L3. GEO database combined with GO and KEGG pathway enrichment were used to analyze the possible interaction genes and functional analysis of DNASE1L3. The function and mechanism of renal fibrosis were studied in vitro by transient transfection of DNASE1L3 knockdown or overexpression in HK-2 cell fibrosis model. Results The expression of DNASE1L3 gene was up-regulated in both in vitro and in vivo models of renal fibrosis. In vitro cell experiments, knockdown of DNASE1L3 promotes epithelial-mesenchymal transition (EMT), and overexpression of DNASE1L3 can effectively inhibit EMT. The results of bioinformatics analysis showed that DNASE1L3 mRNA was related to a variety of immune-related biological processes and inflammatory signaling pathways. Further mechanism studies have found that DNASE1L3 inhibits the progression of renal fibrosis by inhibiting the phosphorylation of signal molecules related to PI3K-AKT pathway. Conclusion DNASE1L3 inhibits the process of renal fibrosis by inhibiting PI3K-AKT signaling pathway, which provides a theoretical basis for the study of the mechanism of renal fibrosis.