title: Protective effects of mesenchymal stromal cells on adriamycin-induced minimal change nephrotic syndrome in rats and possible mechanisms.
abstract: OBJECTIVE
  Minimal change nephrotic syndrome is the most frequent cause of nephrotic syndrome in childhood. Current treatment regimes, which include glucocorticoid hormones and immunosuppressive therapy, are effective and have fast response. However, because of the side effects, long treatment course, poor patient compliance and relapse, novel approaches for the disease are highly desired.
  
  
  METHODS
  The adriamycin-induced nephrotic rat model was established. Rats were allocated to a model group, a prednisone group or mesenchymal stromal cell (MSC) group. Clinical parameters in each treatment group were determined at 2 weeks, 4 weeks and 8 weeks. The messenger RNA (mRNA) levels of synaptopodin, p21 and monocyte chemoattractant protein-1 were determined through the use of quantitative real-time-polymerase chain reaction. Protein levels were determined by means of Western blot or enzyme-linked immunosorbent assay. Podocytes were isolated and apoptotic rate after adriamycin with or without MSC treatment was analyzed by means of flow cytometry.
  
  
  RESULTS
  MSC intervention improved renal function as assessed by urinary protein, blood creatinine and triglyceride levels. MSC intervention reduced adriamycin-induced renal tissue damage visualized by immunohistochemistry and light and electron microscopic analysis and reduced adriamycin-induced podocyte apoptosis. After MSC intervention, mRNA and protein levels of synaptopodin and p21 in renal cortex were significantly increased. MSCs also restored synaptopodin mRNA and protein expression in isolated podocytes. In addition, monocyte chemoattractant protein-1 mRNA in renal cortex and protein level in serum of the MSC treatment group were significantly decreased compared with that in the adriamycin-induced nephropathy model group.
  
  
  CONCLUSIONS
  Our data indicate that MSCs could protect rats from adriamycin-induced minimal change nephrotic syndrome, and the protective effects of MSCs are mediated through multiple actions.
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Guo
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Wu
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Zizhong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Heyi
authors.initials: H
authors.lastname: Hu
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Lianghu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Huiyue
authors.initials: H
authors.lastname: Dong
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Yunfen
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: He
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Shunliang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Lianming
authors.initials: L
authors.lastname: Liao
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Organ Transplant Institute, Fuzhou General Hospital, DongFang Hospital of Xiamen University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, People's Republic of China. Electronic address: tanjm156@yahoo.com.cn.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tan
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004317:Doxorubicin / Q000633:toxicity; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008840:Microfilament Proteins / Q000096:biosynthesis; D009402:Nephrosis, Lipoid / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D011241:Prednisone / Q000008:administration & dosage; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D008840:Microfilament Proteins; D012333:RNA, Messenger; C503969:Synpo protein, rat; D004317:Doxorubicin; D020741:rho GTP-Binding Proteins; D011241:Prednisone
keywords: mesenchymal stromal cells; nephrotic syndrome; p21; synaptopodin