title: Clinicopathological impacts of activated transcription factor c-Jun in peritubular capillary endothelial cells in chronic antibodymediated rejection after kidney transplantation.
abstract: OBJECTIVE
  The transcription factor c-Jun is a major component of the activator protein-1 complex involved in renal physiological events, such as inflammation and fibrosis. We recently demonstrated c-Jun activation in peritubular capillary (PC) endothelial cells and infiltrating cells in acute antibody-mediated rejection after kidney transplantation. However, the clinicopathological role of PC endothelial c-Jun activation has remained undetermined.
  
  
  METHODS
  We investigated endothelial c-Jun activation in PC using phosphorylated c-Jun (p-c-Jun) immunohistochemical staining in 21 cases of chronic active antibody-mediated rejection (CAMR), 14 cases of interstitial fibrosis and tubular atrophy (IF/TA) lacking specific etiology, and 8 normal control subjects (NC).
  
  
  RESULTS
  In CAMR cases, swollen PC endothelial cells showed strong p-c-Jun staining. More p-c-Jun-positive endothelial cells in PC were observed in CAMR than in IF/TA and NC subjects (p < 0.01). These findings were significantly correlated with reduced PC (rs = -0.78, p = 0.0005), the "ci + ct" score of the Banff classification (rs = 0.81, p = 0.0003) and serum creatinine level (rs = 0.48, p = 0.03).
  
  
  CONCLUSIONS
  Endothelial c-Jun activation in PC may contribute to PC loss, interstitial fibrosis and late allograft deterioration in CAMR. These data suggest that c-Jun is an appropriate therapeutic target of CAMR.
authors.affiliation: Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. akimitsu@kk.iij4u.or.jp
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Takamune
authors.initials: T
authors.lastname: Takahashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Horita
authors.forename: Izumi
authors.initials: I
authors.lastname: Yamamoto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
mesh_terms: D000328:Adult; D002196:Capillaries / Q000473:pathology / Q000648:ultrastructure; D002908:Chronic Disease; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008854:Microscopy, Electron; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D016755:Proto-Oncogene Proteins c-jun