Elevated c-kit expression in failed autologous arteriovenous fistulas in end-stage renal disease patients

Abstract

Background: Serum stem cell factor is elevated in end-stage renal disease (ESRD) patients. This study aimed to investigate the expression of the c-kit receptor, which is the specific membrane receptor of stem cell factor, in failed autologous arteriovenous fistulas (AVFs) in end-stage renal disease patients. Methods: A total of 14 ESRD patients with initial AVFs creation and 16 ESRD patients with reconstruction were enrolled in this study. Hematoxylin and eosin (H&E) and elastic Verhoeff-Van Gieson (EVG) staining were used for histomorphometric analyses. Immunohistochemistry was used to examine the expression of c-kit in the intima, and a correlation analysis was performed with the intimal area and the percentage of area stenosis. A double-label immunofluorescence method was used to explore the colocalization of c-kit with α-smooth muscle actin (α-SMA) and CD31. The expression of c-kit and the related PI3K/Akt signaling axis, including PI3K, P-PI3K, Akt, P-Akt473, P-Akt308, and mTOR, was measured by western blotting. Results: Internal elastic lamina (IEL) area, intimal area, percentage of area stenosis, and average optical density (AOD) of c-kit in the intima were significantly higher in the failed group than in the preoperative group ( p ⩽ 0.001). The AOD of c-kit in the intima was positively correlated with the intimal area and the percentage of stenosis (intimal area: R = 0.744, p < 0.001; the percentage of stenosis: R = 0.923, p < 0.001). C-kit colocalized with α-SMA but not with CD31 in studies of c-kit target cells. Moreover, the levels of c-kit and P-PI3K, P-Akt473 and mTOR in the PI3K/Akt axis were also higher in the failed group than in the initial group ( p < 0.05). Conclusions: C-kit and related proteins associated with the PI3K/Akt pathway were elevated in failed AVFs among ESRD patients and that the expression level of c-kit in the intima correlates with the degree of AVF stenosis.