title: Protective effects of FR167653 on chronic allograft nephropathy by inhibiting p38 MAPK in rats.
abstract: BACKGROUND
  Chronic allograft nephropathy (CAN) remains a challenge for transplant clinicians. Some novel intervention strategies may shed new light on its treatment.
  
  
  METHODS
  An orthotopic kidney transplant model in Fisher-to-Lewis rats was used with administration of cyclosporine alone or in combination with FR167653 (30 mg/kg/d subcuntaneously) to recipients. We analyzed renal function and urinary protein excretion. Animals were sacrificed at 30 weeks posttransplantation for histological and immunohistochemical studies.
  
  
  RESULTS
  Renal function among vehicle-treated rats deteriorated progressively with substantial proteinuria compared with FR167653-treated rats. FR167653 administration significantly prevented the morphlogical features of CAN and prolonged rat survivals. p38 mitogen-activated protein kinase (MAPK) expression was markedly reduced by FR167653 treatment. Meanwhile, transforming growth factor-beta1 and monocyte chemotactic protein-1 expression were significantly down-regulated among FR167653-treated hosts.
  
  
  CONCLUSIONS
  p38 MAPK phosphorylation correlated with CAN progression and inhibition of p38 MAPK by FR167653 may provide a potent novel therapeutic target for its prevention.
authors.affiliation: Second Hospital of Hebei Medical University, Department of Nephrology, Shijiazhuang, Hebei Province, PR China. huibintan@163.com
authors.forename: H-B
authors.initials: HB
authors.lastname: Tan
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wu
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D008297:Male; D011507:Proteinuria; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: C104334:FR 167653; D007166:Immunosuppressive Agents; D011720:Pyrazoles; D011725:Pyridines; D016572:Cyclosporine; D003404:Creatinine; D048051:p38 Mitogen-Activated Protein Kinases