The objective of this study was to investigate the effects of the intravenous transplantation of bone marrow mesenchymal stromal cells (BM-MSCs) on alleviating epithelial to mesenchymal transition (EMT) and promoting renal cell differentiation and growth and anti-oxidative stress in rats with gout kidney. Furthermore, the corresponding mechanisms were explored.

A rat model with gout kidney was established by adenine inducing for 4 weeks. Immature male Wistar rats were randomly divided into control group, model group and treatment group. The BM-MSCs treatment group rats were injected with BM-MSCs via tail vein 24 h after the successful modeling, whereas the phosphate-buffered saline model group rats were injected with phosphate-buffered saline (PBS). Six weeks later, urine and blood were collected to assess 24-hour proteinuria, serum creatinine (Scr) and blood urea nitrogen (BUN). Immunohistochemistry was perfomed to determine the expression of transforming growth factor-β1 (TGF-β1). We used Western blot to determine protein expression of P-P38 /P38 and selenium-containing enzyme thioredoxin reductase 1 (TrxR1) in renal tissues. Statistical analysis of differences between the control group and the model group was performed using t-test, and the date of three groups (the control group, the BM-MSCs treatment group, the PBS model group) was calculated using analysis of variance (ANOVA). A value of P<0.05 was considered statistically significant.

Rats with gout kidney induced by adenine were more likely to have mass proteinuria, deterioration of renal function and the histopathologic injury in the kidney, which implied that the gout kidney might evolve into chronic renal failure (CRF). Compared with the PBS model group, the level of indicators in BM-MSCs treatment group was signficantly lower including Scr [(88.90±7.89 μmol/L) vs. (117.40±6.13 μmol/L)], BUN [(7.85±0.88 mmol/L) vs. (10.97±1.03 mmol/L)], 24 hours proteinuria [(27.72±4.90 mg) vs. (54.66±6.72 mg)], TGF-β1 expression[(11.00±2.28) vs. (20.67±1.63)] and the ratio of P-P38 and P38 [(0.31±0.09 μmol/L) vs. (0.50±0.13 μmol/L)]. However, the ratio of TrxR1 and β-actin was increased in BM-MSCs treatment group [(0.80±0.19 μmol/L) vs. (0.41±0.23 μmol/L)].

BM-MSCs could alleviate the renal damages of adenine-induced gout kidney/chronic renal failure and improve the renal function by increasing the expression of TrxR1 which could promote renal cell differentiation and growth and anti-oxidative stress, or by decreasing the level of TGF-β1 that contributed to alleviating EMT, which wass mediated through supressing TNF-α/P38 signaling pathway.