Mesenchymal stem cells (MSCs) are shown to alleviate renal injury of diabetic nephropathy (DN) in rats. However, the underlying mechanism of this beneficial effect is not fully understood. The aims of this study are to evaluate effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on renal cell apoptosis in streptozotocin- (STZ-) induced diabetic rats and explore the underlying mechanisms. Characteristics of UC-MSCs were identified by flow cytometry and differentiation capability. Six weeks after DN induction by STZ injection in Sprague-Dawley rats, the DN rats received UC-MSCs once a week for consecutive two weeks. DN-related physical and biochemical parameters were measured at 2 weeks after UC-MSC infusion. Renal histological changes were also assessed. Moreover, the apoptosis of renal cells and expression of apoptosis-related proteins were evaluated. Compared with DN rats, rats treated with UC-MSCs showed suppressed increase in 24-hour urinary total protein, urinary albumin to creatinine ratio, serum creatinine, and blood urea nitrogen. UC-MSC treatment ameliorated pathological abnormalities in the kidney of DN rats as evidenced by H&E, PAS, and Masson Trichrome staining. Furthermore, UC-MSC treatment reduced apoptosis of renal cells in DN rats. UC-MSCs promoted expression of antiapoptosis protein Bcl-xl and suppressed expression of high mobility group protein B1 (HMGB1) in the kidney of DN rats. Most importantly, UC-MSCs suppressed upregulation of thioredoxin-interacting protein (TXNIP), downregulation of thioredoxin 1 (TRX1), and activation of apoptosis signal-regulating kinase 1 (ASK1) and P38 MAPK in the kidney of DN rats. Our results suggest that UC-MSCs could alleviate nephrocyte injury and albuminuria of DN rats through their antiapoptotic property. The protective effects of UC-MSCs may be mediated by inhibiting TXNIP upregulation in part.

中文翻译：

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脐带来源的间充质干细胞可改善糖尿病性肾病大鼠模型中的肾细胞损伤和蛋白尿。

间充质干细胞（MSCs）可以减轻大鼠糖尿病性肾病（DN）的肾脏损伤。但是，尚未完全了解这种有益效果的潜在机制。这项研究的目的是评估脐带间充质干细胞（UC-MSCs）对链脲佐菌素（STZ-）诱导的糖尿病大鼠肾细胞凋亡的影响，并探讨其潜在机制。通过流式细胞仪和分化能力鉴定了UC-MSCs的特征。在Sprague-Dawley大鼠中，通过STZ注射诱导DN后六周，DN大鼠每周两次接受UC-MSC，连续两周。在输注UC-MSC后2周测量与DN相关的物理和生化参数。还评估了肾脏的组织学变化。此外，评估肾细胞的凋亡和凋亡相关蛋白的表达。与DN大鼠相比，用UC-MSC治疗的大鼠显示24小时尿总蛋白，尿白蛋白与肌酐之比，血清肌酐和血尿素氮的增加受到抑制。H＆E，PAS和Masson Trichrome染色证明，UC-MSC治疗可改善DN大鼠肾脏的病理异常。此外，UC-MSC处理可减少DN大鼠肾细胞的凋亡。UC-MSCs在DN大鼠的肾脏中促进抗凋亡蛋白Bcl-xl的表达并抑制高迁移率族蛋白B1（HMGB1）的表达。最重要的是，UC-MSC抑制了硫氧还蛋白相互作用蛋白（TXNIP）的上调，硫氧还蛋白1（TRX1）的下调，肾大鼠肾脏中凋亡信号调节激酶1（ASK1）和P38 MAPK的激活和激活 我们的结果表明，UC-MSCs通过其抗凋亡特性可以减轻DN大鼠的肾细胞损伤和蛋白尿。UC-MSC的保护作用可以通过部分抑制TXNIP上调来介导。