Hsa-miR-371-5p inhibits human mesangial cell proliferation and promotes apoptosis in lupus nephritis by directly targeting hypoxia-inducible factor 1α

MicroRNAs (miRNAs/miR) have emerged as a novel class of gene expression modulators in kidney disease. Lupus nephritis (LN) is the predominant cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Hsa-miR-371-5p has previously been reported to be dysregulated in LN using a miRNA microarray analysis. The present study aimed to determine the function and molecular mechanisms of hsa-miR-371-5p in human mesangial cells of LN. Quantitative polymerase chain reaction (qPCR) was used to detect hsa-miR-371-5p expression in LN tissues. Furthermore, the MTT assay and flow cytometric analyses were performed to analyze the effects of hsa-miR-371-5p on mesangial cell proliferation and apoptosis. Bioinformatics analysis, luciferase reporter assay, qPCR and western blotting were also conducted to predict and confirm the target gene of hsa-miR-371-5p in mesangial cells. The results demonstrated that hsa-miR-371-5p expression was markedly downregulated in LN renal tissues compared with in normal kidney tissues. Restoration of hsa-miR-371-5p expression using synthetic hsa-miR-371-5p mimics was able to significantly inhibit mesangial cell proliferation and induce apoptosis. In addition, mechanistic exploration demonstrated that hypoxia-inducible factor la (HIF-1 alpha) was a direct target gene of hsa-miR-371-5p in mesangial cells. In conclusion, these results suggested that hsa-miR-371-5p is downregulated in LN, and overexpression of hsa-miR-371-5p may inhibit mesangial cell proliferation and promote apoptosis by directly targeting HIF-1 alpha.