Clinicopathological impacts of activated transcription factor c-Jun in peritubular capillary endothelial cells in chronic antibodymediated rejection after kidney transplantation

Abstract

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. 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). 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). 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.