Center of Excellence and Cancer Genome, Mansoura Urology and Nephrology Center, 35516, Egypt.
Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Life Sci. 2021 May 1;272:119221. doi: 10.1016/j.lfs.2021.119221. Epub 2021 Feb 17.
The present study aimed to investigate the invitro preconditioning of adipose-derived mesenchymal stem cells (ADMSCs) with CD44-targeted hyalournic acid (HA) on ischemic kidney injury in rats. Ninety male Sprague Dawley rats were randomly allocated into the following groups; i) sham group, ii) control group: rats exposed to 45 min left renal ischemia with saline treatment, iii) HA group as control group but rats treated with HA, iv) ADMSCs group as control but rats treated with ADMSCs v) HA + ADMSCs group as ADMSCs but rats treated with ADMSCs preconditioned with CD44-tageted HA for 14 days. We found that treattment with either ADMSCs or HA + ADMSCs caused significant decrease in the elevated serum creatinine and BUN and malondialdehyde (MDA) concentrations and expression of TGF-β1, fibronectin, collagen type I, inducible nitric oxide synthease (iNOS) and microRNAs (miR-21, miR-17-5p, miR-10a) in kidney and significant increase in creatinine clearance, superoxide dismutase (SOD), reduced glutathione (GSH) and the expression of Bcl2, vascular endothelial growth factor (VEGF), Wnt/β-catenin pathway genes in kidney compared to control group (p < 0.05). Moreover, HA + ADMSCs group caused more significant improvement in these parameters than ADMSCs group (p < 0.05), while HA group did not cause any significant improvement in these parameters compared to control group. These results suggest that preconditioning of ADMSCs preconditioned with CD44-targted HA enhanced their cytoprotective effect against ischemic kidney injury. This renoprotective effect might be due to activation of angiogenesis, Wnt/β-catenin pathway proteins, and suppression of oxidative stress, apoptosis, inflammation and fibrosis.
本研究旨在探讨 CD44 靶向透明质酸（HA）预处理脂肪间充质干细胞（ADMSCs）对大鼠缺血性肾损伤的体外作用。90 只雄性 Sprague Dawley 大鼠随机分为以下 5 组：i）假手术组；ii）对照组：大鼠暴露于左侧肾缺血 45 分钟，用生理盐水处理；iii）HA 组：作为对照组，大鼠用 HA 处理；iv）ADMSCs 组：作为对照组，大鼠用 ADMSCs 处理；v）HA+ADMSCs 组：用 CD44 靶向 HA 预处理 14 天的 ADMSCs 处理。我们发现，ADMSCs 或 HA+ADMSCs 治疗均可显著降低升高的血清肌酐和 BUN 及丙二醛（MDA）浓度，降低 TGF-β1、纤维连接蛋白、I 型胶原、诱导型一氧化氮合酶（iNOS）和微小 RNA（miR-21、miR-17-5p、miR-10a）的表达，增加肌酐清除率、超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）及 Bcl2、血管内皮生长因子（VEGF）、Wnt/β-catenin 通路基因的表达，与对照组相比（p<0.05）。此外，HA+ADMSCs 组比 ADMSCs 组更显著地改善了这些参数（p<0.05），而 HA 组与对照组相比，这些参数没有任何显著改善。这些结果表明，CD44 靶向 HA 预处理 ADMSCs 增强了其对缺血性肾损伤的细胞保护作用。这种肾保护作用可能是由于血管生成、Wnt/β-catenin 通路蛋白的激活，以及氧化应激、细胞凋亡、炎症和纤维化的抑制。
