Bone Marrow Mesenchymal Stem Cells Ameliorate Diabetes and Diabetic Renal Fibrosis by Modulating the Inflammatory Factor IL-11.

Li-Lan Huang, Ji Yang, Yue-Yuan Hou, Yi-Hua Bai, Hong-Ying Jiang
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Abstract

Objective: This study aims to explore the therapeutic potential of mesenchymal stem cells (MSC) in treating diabetic nephropathy (DN) by investigating their effect on IL-11 modulation in a mouse model.

Methods: The effects of MSC therapy on DN were examined both in vivo and in vitro. Sixty adult male C57BL/6 mice were divided into the streptozotocin (STZ) diabetes (T1D) and the high-fat diet diabetes (T2D) models, with both groups receiving MSC treatment or saline for 4 or 8 weeks. Blood glucose, serum urea, interleukin-11 (IL-11), and kidney fibrosis markers were measured. Additionally, western blotting was used to assess levels of Type I and III collagen, E-Cadherin, α- smooth muscle actin (α-SMA), Vimentin, and ferroptosis suppressor protein 1 (FSP-1).

Results: MSC-treated T1D and T2D mice showed reduced blood glucose, serum urea, IL-11, TGF-β, and fibrosis markers (type I and III collagen, α-SMA, Vimentin, FSP-1), alongside increased E-Cadherin expression. Similar effects were observed in vitro using mouse glomerular epithelial cells, confirming MSC-mediated suppression of fibrosis pathways.

Conclusion: MSC therapy improves nephropathy, likely by inhibiting IL-11 and reducing fibrosis- related markers, making it a promising treatment for DN.

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骨髓间充质干细胞通过调节炎症因子IL-11改善糖尿病和糖尿病肾纤维化。
目的:通过研究间充质干细胞(MSC)在小鼠模型中对IL-11调节的影响,探讨其治疗糖尿病肾病(DN)的潜力。方法:在体内和体外观察MSC治疗DN的作用。将60只成年雄性C57BL/6小鼠分为链脲霉素(STZ)型糖尿病(T1D)和高脂饮食型糖尿病(T2D)模型,两组分别给予MSC治疗或生理盐水治疗4周和8周。测定血糖、血清尿素、白细胞介素-11 (IL-11)、肾纤维化指标。此外,western blotting检测I型和III型胶原蛋白、E-Cadherin、α-平滑肌肌动蛋白(α- sma)、Vimentin和铁下垂抑制蛋白1 (FSP-1)的水平。结果:mscs处理的T1D和T2D小鼠血糖、血清尿素、IL-11、TGF-β和纤维化标志物(I型和III型胶原、α-SMA、Vimentin、FSP-1)降低,E-Cadherin表达增加。使用小鼠肾小球上皮细胞在体外观察到类似的效果,证实了msc介导的纤维化途径的抑制。结论:MSC治疗可能通过抑制IL-11和降低纤维化相关标志物来改善肾病,使其成为DN的一种有希望的治疗方法。
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