title: Activation of the transcription factor c-Jun in acute cellular and antibody-mediated rejection after kidney transplantation.
abstract: c-Jun is a transcription factor that belongs to the activator protein-1 family of proteins. In human kidney disease, c-Jun is activated in glomerular and tubular cells and plays a major role in renal pathophysiology. However, the contribution of this pathway to renal allograft rejection has not been determined. We investigated whether c-Jun is activated in acute allograft rejection. c-Jun activation was assessed with immunohistochemistry using phospho-specific c-Jun antibodies in control human renal tissue and renal tissue from patients with acute cellular rejection, acute antibody-mediated rejection, and no rejection in the month after transplantation. In patients with acute cellular rejection, c-Jun activation was observed primarily in infiltrated T cells associated with tubulitis, interstitial cell infiltration, and endarteritis. The number of infiltrated phosphorylated c-Jun-positive cells in the tubules and interstitium was correlated with the Banff classification "t" and "i" scores. In patients with acute antibody-mediated rejection, c-Jun activation was observed in injured endothelial cells as well as in infiltrated cells, including macrophages, in the glomerular and peritubular capillaries. Furthermore, the serum creatinine levels and changes in serum creatinine from the previous year were significantly correlated with the total tubulointerstitial phosphorylated c-Jun-positive score (representing the number of positive nuclei in the tubules, interstitium, and peritubular capillaries). In conclusion, c-Jun was activated in acute antibody-mediated rejection and acute cellular rejection and was associated with reduced graft function. These findings suggest that c-Jun plays a key role in pathological events and may represent a novel therapeutic target in acute renal allograft rejection.
authors.affiliation: Division of Kidney and Hypertension, 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: Satoshi
authors.initials: S
authors.lastname: Teraoka
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamaguchi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000906:Antibodies / Q000276:immunology*; D001706:Biopsy; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000906:Antibodies; D016755:Proto-Oncogene Proteins c-jun; D048670:MAP Kinase Kinase 4