MiR-539 Inhibits Inflammation in Renal Transplant Iscemia-Reperfusion Injury Via Blocking the MyD88/NF-κB Pathway

Abstract

Objective: This study was conducted in order to investigate the anti-inflammatory effects of miR-539 on renal transplant ischemia-reperfusion (I/R) injury. Methods: A mouse model replicating renal transplant I/R injury and a cellular model of oxygen-glucose deprivation (OGD) treatment were established. The blood urea nitrogen (BUN) levels were determined for all models. The miR-539 expressions were detected in the kidney tissues and HK-2 cells following the different transfections using qRT-PCR. Western blotting was used to analyze myeloid differentiation factor 88 (MyD88), as well as the unphosphorylated and phosphorylated Nuclear factor-κB (NF-κB) protein expressions. The interactions between miR-539 and MyD88 were examined through a luciferase reporter assay. Moreover, pro-inflammatory cytokines levels, including the tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8, were measured using an enzyme-linked immunosorbent assay (ELISA). A renal tubular necrosis score (TNS) was employed as a means of assessing the renal function of mouse model. Results: miR-539 was downregulated during renal I/R injury. In vitro , miR-539 relieved the secretion of pro-inflammatory cytokines. A luciferase reporter assay demonstrated that MyD88 was a direct target of miR-539. Further investigation revealed that miR-539 inhibited I/R injury-induced inflammation by downregulating the MyD88/NF-κB pathway. It was shown that miR-539 exerted anti-inflammatory effects in the mice that underwent renal transplant I/R injury. Conclusion: MiR-539 alleviated inflammation in renal transplant I/R injury through the MyD88/NF-κB pathway.