miR-6516-3p-mediated downregulation of the endogenous MMP-9 inhibitor RECK in mesangial cells might exacerbate lupus nephritis.

Background: MicroRNAs (miRNAs) regulate biological processes by inhibiting translation and causing mRNA degradation. In this study, we identified the miRNAs involved in the development and progression of lupus nephritis (LNs) and verified their roles.

Methods: Total RNA, extracted from PBMCs collected from patients with LNs before and after treatment, was used for miRNA array analysis to identify miRNAs whose expression was significantly altered. The results of this analysis were confirmed using qRT-PCR. The identified miRNAs were transfected into normal human mesangial cells (NHMCs), human renal proximal tubule epithelial cells (RPTECs), human umbilical vein endothelial cells (HUVECs), and THP-1-derived macrophages (THP1-Mφ) to investigate their biological functions.

Results: Three miRNAs were altered in PBMCs before and after treatment of LNs. Among these miRNAs, hsa-miR-6516-3p promoted TNF-α-induced expression of MMP-9 in NHMCs. Moreover, hsa-miR-6516-3p downregulated the expression of RECK, an endogenous inhibitor of MMP-9. However, in NHMCs, endogenous hsa-miR-6516-3p was not present in functional amounts under inflammatory environment; therefore, we performed analysis using an experimental system considering extracellular influences of mesangial cells under LNs. The expression of hsa-miR-6516-3p was increased in HUVECs under inflammatory conditions and in activated macrophages.

Conclusions: hsa-miR-6516-3p increases MMP9 expression by suppressing RECK, and might, thereby, exacerbate LNs.