P0987MIR-181A IMPROVED RENAL INFLAMMATION VIA TARGETING TNF-Α IN DIABETIC NEPHROPATHY

Abstract

Abstract Background and Aims Recent studies have revealed that miR-181a is involved in various inflammation associated diseases, however, its participation in pathogenesis of diabetic nephropathy (DN) remains unclear. Hence, we investigated the involvement of miR-181a in the pathogenesis of DN patients and in animal model. Method miR-181a level was measured in the kidney of DN patients and DN mice model (db/db mice) by RT-PCR. To investigate the interaction of miR-181 a with the 3’-UTR of potential target transcripts, Luciferase reporter assays were performed. miR-181a-GFP-AAV and miR-181a inhibitor was generated to over-express or downregulate miR-181a in the kidney of db/db mice respectively. The expression of target gene and inflammatory proteins were measured in the kidney of our animal model. Results In DN patients and DN mice, a significant decrease in miR-181a levels in kidney were revealed by Expression analyses performed. Overexpression of miR-181a reduced proinflammatory genes (TNF-ɑ, IL-1β, and IL-18 ) expression, whereas suppression of miR-181a worsened these changes. Furthermore, there was a negative linear correlation between miR-181a and TNF-ɑ, IL-1β, and IL-18 expression levels in the kidney from DN patients. Luciferase assays revealed TNF-ɑ as a direct target of miR-181a. Conclusion Our data emphasized on the anti-inflammatory actions of miR-181a via targeting TNF-ɑ in the context of renal inflammation in DN. Hence, miR-181a could be served as a potential therapeutic options for controlling renal inflammation in DN.