Inhibiting Rab27a Expression In Renal Tubular Epithelial Cells Improves The Inflammatory Of Diabetic Kidney Disease Through The MiR-26a-5p/CHAC1/NF-kB Pathway

Background:Initially,exosomes were thought to be the cellular trash.Later,exosomes were found to mediate intercellular communication,and following a flood of research on exosomal receptor cells,but the effect of exosomes on donor cells remains unclear.It has been reported exosomes secreted by renal proximal tubular epithelial cells(PTECs)under different stimuli accelerated the progress of acute and chronic kidney diseases.Purpose:The purpose of this study was to investigate whether silencing the expression of Rab27a in renal tubular epithelial cells which could inhibit exosome secretion on renal tubular epithelial cells could improve the inflammation of diabetic kidney disease.Method and result:First,we prove that the silence Rab27a can inhibit BSA-induced the secretion of inflammatory cytokines from the renal tubular epithelial cells,immunohistochemical staining in HFD/STZ-induced diabetic mouse model verified again Rab27a expression and inflammatory biomarkers in IL-6 and TNF-a and fibrosis biomarkers COL-1 expression level is consistently significantly higher.In addition,we also demonstrated that the expression of miR-26a-5p in exosomes secreted by renal tubular epithelial cells was significantly increased under the stimulation of BSA,while inhibition of the expression of Rab27a in renal tubular epithelial cells increased the accumulation of miR-26a-5p in renal tubular epithelial cells.Next,we confirmed that overexpression of miR-26a-5p could inhibit the secretion of BSA-induced inflammatory cytokines in renal tubular epithelial cells,and we also found that silencing of miR-26a-5p could promote the secretion of BSA-induced inflammatory cytokines in renal tubular epithelial cells by inhibiting the expression of miR-26a-5p.Then we found through TargetScan that miR-26a-5p can directly target the 3'-UTR of CHAC1,which was proved by Dual-Glo(?)Luciferase Assay System.Next,we proved that silencing CHAC1 can inhibit the secretion of BSA-induced inflammatory factors in renal tubular epithelial cells,overexpression of miR-26a-5p can inhibit the expression of CHAC1,and silencing miR-26a-5p can promote the expression of CHAC1.Silencing CHAC1 inhibited miR-26a-5p inhibitor-induced the secretion of inflammatory cytokines in renal tubular epithelial cells.Moreover,silencing miR-26a-5p promoted the activation of NF-kB signaling pathway,which-was blocked by siCHAC1.Conclusion:Therefore,we conclude that by inhibiting exosome secretion of renal tubular epithelial can promote miR-26a-5p accumulation in renal tubular epithelial which can inhibit of CHCA1 expression lead to suppression of NF-kB signaling pathway in turn suppress BSA-induced the secretion of inflammatory cytokines from the renal tubular epithelial cells,may through this channel to improve the progress of diabetic nephropathy inflammation.Our study provides a new insight for the pathogenesis of diabetic kidney disease and a new target for its treatment.