Renal Tubulointerstitial Fibrosis And Th17/Treg Imbalance In UUO Rat Model Following PMSC Infusion

Objective: In search of the effects of placenta mesenchymal stem cells(PMSC) onrenal tubulointerstitial fibrosis induced by obstructive nephropathy and a potentialchange in Th17/Treg balance in a rat model. Methods:54Wistar rats were randomlydivided into PMSC intervention group,normal saline infusion group and shamoperation group.Obstructive nephropathy models were established in rats of PMSCintervention group and normal saline infusion group by unilateral ureteralobstruction(UUO). Peripheral blood, renal tissue and spleen samples were collectedon3d,7d and14d after model establishment. Treg and Th17frequencies weremeasured by flow cytometry. Renal Foxp3expressions were assessed byimmunohistochemical method. Morphology and collagen deposition in rat kidneywere observed by PAS and Masson staining respectively. Inflammatory cytokines,including IL-4、IL-6、IL-10、IL-17A、IFN-γ、TGF-βin the peripheral blood andrenal tissue homogenate were detected using an ELISA method. Results: AfterUUO,CD4+CD25+T cell/CD4+T cell in peripheral blood and IL17A+IFNγ-CD4+Tcell/CD4+Tcell in spleen were significantly higher than that in sham operationgroup(P<0.05), while there were no significant difference between PMSC interventiongroup and normal saline infusion group(P>0.05).14days after modelestablishment,Foxp3expressed in PMSC intervention group was significantly higherthan the other groups(P<0.05).3days and14days after model establishment, theextent of renal tubulointerstitial fibrosis in PMSC intervention group was less severethan that in normal saline infusion group(P<0.05).After UUO, the expression level ofTGF-β、IFN-γ、IL-6rose, meanwhile IL-4、IL-10dropped.In addition to that, ahigh variability of IL-17. PMSC intervention group showed less TGF-β3days andhigher IL-1014days after model establishment than saline infusion grouprespectively. Conclusion: PMSC therapy can bring positive effect to obstructivekidney and might alleviate renal tubulointerstitial fibrosis progression. It might partlybe explained by the involvement of Th17/Treg balance, the increase of foxp3expression in local renal tissue, lower level of anti-fibrosis cytokine TGF-βandhigher level of anti-inflammation cytokine IL-10.