Selenium-Binding Protein-1 in Smooth Muscle Cells is Downregulated in a Rhesus Monkey Model of Chronic Allograft Nephropathy

Authors
Jose R. TorrealbaMatthew ColburnSusan GolnerZhen ChangTara ScheunemannJohn H. FechnerDrew RoenneburgHuaizhong HuTausif AlamHyoung T. KimTuran KanmazTerry OberleyStuart JKnechtleMajed M. Hamawy
Department
Dept. of Surgery (외과학)
Issue Date
2005
Citation
American Journal of Transplantation, Vol.5(1) : 58-67, 2005
ISSN
1600-6135
Abstract
Treating patients with kidney failure by organ trans- plantation has been extraordinarily successful. Al- though, current immunosuppressants have improved short-term allograft survival, most transplants are eventually lost due to chronic allograft nephropathy (CAN). The molecular mechanisms underlying CAN are poorly understood. Smooth muscle cells (SMC) play a major role in the pathogenesis of CAN by contributing to the thickening of the intima and narrowing of the lu- men of blood vessels. We show that selenium-binding protein-1 (SBP-1), a protein implicated in protein traf- ficking and secretion, is localized primarily to SMC in vivo. SBP-1 was heavily tyrosine-phosphorylated in vivo. Remarkably, SBP-1 was absent or strongly downregulated in vascular SMC in monkey kidney al- lografts with CAN. In contrast, the SMC a -actin was strongly expressed in the vascular SMC of the same al- lografts, indicating that the decrease in SBP-1 was not due to a global decrease in SMC proteins. Out of four growth factors implicated in the pathogenesis of CAN, only TGF-b blocked the expression of SBP-1; thus, TGF-b could regulate the expression of SBP-1 in CAN. These results show that SBP-1 localizes primarily to SMC in vivo and implicate this phosphoprotein in the effects of TGF-b on SMC and in the process of CAN. Key words: Chronic allograft nephropathy, trans- plantation, smooth muscle, selenium-binding protein- 1, vascular rejection, atherosclerosis
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/34953
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
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