Mesenchymal Stem Cells Ameliorate Uric Acid Induced Nephropathy in Rats

Abstract

BackgroundThe elevation of serum uric acid (UA) is positively correlated to the incidence and mortality of kidney diseases by evoked inflammation and epithelial‐mesenchymal transition (EMT) in renal tubular epithelial cells. Mesenchymal stem cells (MSCs) are able to facilitate immunomodulation and repair kidney injury in experimental models of acute or chronic kidney injury. Our study aims to investigate the effects of MSCs on kidney injury both in rats model of uric acid nephropathy and high uric acid‐treated renal tubular epithelial cells (NRK‐52E).MethodsIn vivo, rats were intragastric administrated with potassium oxonate (PO, 1500 mg/kg/day) plus adenine (Ad, 50 mg/kg/day) for 4 w to develop hyperuricemia. MSCs treatment (tail vain injection of MSCs 3×106 cells/rat) was conducted from the 2nd week for 2 times with one week interval. After 6 weeks, the kidney tissues were collected for further detections. In vitro, NRK‐52E cells were co‐cultured with or without MSCs in Transwell system. Cell cycle and apoptosis were analyzed by flow cytometry. The mRNA and protein expression of genes related to inflammation and fibrosis were detected by q‐PCR and WB.Results MSCs alleviated kidney injury in rats of uric acid nephropathy. Compared with UA group, HE and Masson staining have shown that the histological abnormalities and fibrosis were significantly ameliorated after MSCs treatment. Moreover, the mRNA of FN, TNF‐α, TGF‐β and IL‐1β showed marked decrease in UA + MSCs group in comparison to UA group. MSCs inhibited cellular damage in high uric acid‐treated NRK‐52E. Comparing with high uric acid group, MSCs co‐culture induced remarkable increase of cell proliferation index (62.61% vs. 54.55%), slight decreased of apoptosis rate (3.7% vs. 4.8%) and increased expression of anti‐apoptotic protein Bcl‐2. In respect of the expression of inflammation and fibrosis related protein, MSCs co‐culture slightly downregulated the expression of TNF‐α, α‐SMA and FN, while upregulated the expression of E‐cad, but no significant change was observed on VCAM‐1. ConclusionDuring the development of hyperuricemia, MSCs effectively ameliorated inflammatory infiltration, suppressed the fibrosis progress trigged by inflammatory factors and fibrosis factor as TGF‐β, resulting in the improvement of high uric acid induced kidney lesion. MSCs exerted the protective role through increase of cell viability and proliferation, decrease of apoptosis and the expression of inflammatory factor TNF‐α, and increase the expression of E‐cad, which contributed to the suppression of interstitial transformation of renal tubular epithelial cells.Support or Funding InformationThis study was supported by the Program of National Natural Science Foundation of China (81370824), and the National Key Clinical Project.