Factors Implicated in the Expression of Selenium Binding Protein 1 in Chronic Allograft Vasculopathy
Pathology, University of Texas Southwestern Medical Center, Dallas, TX
Surgery, University of Wisconsin, Madison, WI
Medicine, University of Wisconsin, Madison, WI
Meeting: 2013 American Transplant Congress
Abstract number: B956
Background: Selenium binding protein-1 (SBP-1) has been implicated in intracellular protein trafficking and secretion. In a rhesus monkey kidney transplant model we previously demonstrated that SBP-1 is significantly downregulated in the smooth muscle cells (SMC) of arteries with chronic allograft vasculopathy (CAV).
Objective: The purpose of this study were multiple: 1- to investigate the expression of SBP-1 in human and murine allografts with chronic vasculopathy; 2- to explore factors that influence the expression of SBP-1 in vitro; and 3-to asses the influence of selenium supplementation in SBP-1 levels in mice.
Methods: 21 biopsies from human kidney allografts and mouse heart transplants -B10.A/B10.BR model- were immunolabeled with antibodies that recognize SBP-1 in paraffin tissue. CRL-1999 SMC cell cultures were incubated and assess for the expression of SBP-1 in the presence of PDGF, INF-Γ, TNF-Α and TGF-Β. Selenium (Se) supplementation (sodium selenite) was given for 3 months to nude mice that were evaluated for the effect of Se in the expression of SBP-1 in kidneys.
Results: Using a semiquantitative scale (0-3 for SBP-1 signal) the average staining for SBP-1 in control biopsies with normal vessels was 2.89, whereas for biopsies with any degree of CAV was 1.33 (p<0.001). SBP-1 was significantly decreased in each study group when compared to controls: humans p<0.02 and mice p<0.03. A significant negative correlation between the degree of CAV and the SBP-1 staining was found (r= -0.97). After 48 hours of incubation at 37C of the SMC cell line, only TGF-Β induced downregulation of SBP-1. Whereas the supplementation of Se in the diet increased the levels of anti-oxidant selenoproteins GPX-1, 2 and 3; it had no effect on the levels of SBP-1 on Western blots of kidneys from nude mice.
Conclusions: SBP-1 is significantly downregulated in the vascular smooth muscle of vessels with CAV, an effect that seems to be induced by TGFΒ in vitro. These fidnings implicate SBP-1 in the pathogenesis of CAV.
To cite this abstract in AMA style:
Torrealba J, Roenneburg D, Djamali A. Factors Implicated in the Expression of Selenium Binding Protein 1 in Chronic Allograft Vasculopathy [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/factors-implicated-in-the-expression-of-selenium-binding-protein-1-in-chronic-allograft-vasculopathy/. Accessed May 14, 2025.« Back to 2013 American Transplant Congress