Hu Junping, Zhu Qing, Xia Min, Guo Tai L, Wang Zhengchao, Li Pin-Lan, Han Wei-Qing, Yi Fan, Li Ningjun
Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, USA.
Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, People's Republic of China.
J Mol Med (Berl). 2014 Nov;92(11):1139-45. doi: 10.1007/s00109-014-1199-1. Epub 2014 Aug 19.
Adult stem cell deficiency has been implicated in the pathogenic mechanism for various diseases. Renal medullary dysfunction is one of the major mechanisms for the development of hypertension in Dahl salt-sensitive (S) rats. The present study first detected a stem cell deficiency in the renal medulla in Dahl S rats and then tested the hypothesis that transplantation of mesenchymal stem cells (MSCs) into the renal medulla improves salt-sensitive hypertension in Dahl S rats. Immunohistochemistry and flowcytometry analyses showed a significantly reduced number of stem cell marker CD133+ cells in the renal medulla from Dahl S rats compared with controls, suggesting a stem cell deficiency. Rat MSCs or control cells were transplanted into the renal medulla in uninephrectomized Dahl S rats, which were then treated with a low- or high-salt diet for 20 days. High-salt-induced sodium retention and hypertension was significantly attenuated in MSC-treated rats compared with control cell-treated rats. Meanwhile, high-salt-induced increases of proinflammatory factors, monocyte chemoattractant protein-1, and interleukin-1β, in the renal medulla were blocked by MSC treatment. Furthermore, immunostaining showed that high-salt-induced immune cell infiltration into the renal medulla was substantially inhibited by MSC treatment. These results suggested that stem cell defect in the renal medulla may contribute to the hypertension in Dahl S rats and that correction of this stem cell defect by MSCs attenuated hypertension in Dahl S rats through anti-inflammation.
Stem cell defect in the renal medulla may contribute to salt-sensitive hypertension Stem cell therapy is a potential therapeutic strategy for salt-sensitive hypertension Normal stem cell inhibits the inflammatory response to high salt in the renal medulla.
成体干细胞缺陷已被认为与多种疾病的发病机制有关。肾髓质功能障碍是Dahl盐敏感（S）大鼠高血压发生的主要机制之一。本研究首先检测了Dahl S大鼠肾髓质中的干细胞缺陷，然后检验了将间充质干细胞（MSC）移植到肾髓质中可改善Dahl S大鼠盐敏感性高血压的假说。免疫组织化学和流式细胞术分析显示，与对照组相比，Dahl S大鼠肾髓质中干细胞标志物CD133+细胞的数量显著减少，提示存在干细胞缺陷。将大鼠MSC或对照细胞移植到单侧肾切除的Dahl S大鼠的肾髓质中，然后用低或高盐饮食处理20天。与对照细胞处理的大鼠相比，MSC处理的大鼠中高盐诱导的钠潴留和高血压明显减轻。同时，MSC处理可阻断高盐诱导的肾髓质中促炎因子、单核细胞趋化蛋白-1和白细胞介素-1β的增加。此外，免疫染色显示，MSC处理可显著抑制高盐诱导的免疫细胞浸润到肾髓质中。这些结果表明，肾髓质中的干细胞缺陷可能导致Dahl S大鼠的高血压，而通过MSC纠正这种干细胞缺陷可通过抗炎作用减轻Dahl S大鼠的高血压。
肾髓质中的干细胞缺陷可能导致盐敏感性高血压 干细胞治疗是盐敏感性高血压的一种潜在治疗策略 正常干细胞抑制肾髓质对高盐的炎症反应
