title: Transplantation of mesenchymal stem cells into the renal medulla attenuated salt-sensitive hypertension in Dahl S rat.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, USA.
authors.forename: Junping
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, USA.
authors.forename: Tai L
authors.initials: TL
authors.lastname: Guo
authors.affiliation: Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, People's Republic of China.
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, USA.
authors.forename: Pin-Lan
authors.initials: PL
authors.lastname: Li
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, USA.
authors.forename: Wei-Qing
authors.initials: WQ
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yi
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, USA. nli@vcu.edu.
authors.forename: Ningjun
authors.initials: N
authors.lastname: Li
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000818:Animals; D062186:Arterial Pressure; D006973:Hypertension / Q000503:physiopathology / Q000628:therapy*; D007249:Inflammation; D007679:Kidney Medulla / Q000187:drug effects; D051917:Leukosialin / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D018800:Thy-1 Antigens / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D051917:Leukosialin; D050814:Octamer Transcription Factor-3; C000606025:Prom1 protein, rat; D017673:Sodium Chloride, Dietary; D018800:Thy-1 Antigens
keywords: CD133; Immune cell; Inflammation