title: Induction of C-Mip by IL-17 Plays an  Important Role in Adriamycin-Induced  Podocyte Damage.
abstract: OBJECTIVE
  Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear.
  
  
  METHODS
  The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN) mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes.
  
  
  RESULTS
  The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down-regulation of phosphor-nephrin, and an increased binding of c-mip to NF-κB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-κB/RelA in IL-17 treated cells. Persistent activation of NF-κB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level.
  
  
  CONCLUSIONS
  These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Su
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Lin
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Peng
authors.initials: P
authors.lastname: You
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Fan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000276:immunology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004317:Doxorubicin / Q000009:adverse effects*; D020381:Interleukin-17 / Q000032:analysis / Q000097:blood / Q000276:immunology*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology; D050199:Podocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; C551587:Cmip protein, mouse; D016207:Cytokines; D020381:Interleukin-17; D016328:NF-kappa B; D004317:Doxorubicin