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Selenium-binding protein-1 in smooth muscle cells is downregulated in a rhesus monkey model of chronic allograft nephropathy. Am J Transplant 2005 Jan;5(1):58-67

Date

01/08/2005

Pubmed ID

15636612

DOI

10.1111/j.1600-6143.2004.00651.x

Abstract

Treating patients with kidney failure by organ transplantation has been extraordinarily successful. Although, 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 lumen of blood vessels. We show that selenium-binding protein-1 (SBP-1), a protein implicated in protein trafficking 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 allografts with CAN. In contrast, the SMC alpha-actin was strongly expressed in the vascular SMC of the same allografts, 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-beta blocked the expression of SBP-1; thus, TGF-beta 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-beta on SMC and in the process of CAN.

Author List

Torrealba JR, Colburn M, Golner S, Chang Z, Scheunemann T, Fechner JH, Roenneburg D, Hu H, Alam T, Kim HT, Kanmaz T, Oberley T, Knechtle SJ, Hamawy MM

Author

Tara L. Petersen MD, MSED Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Actins
Animals
Carrier Proteins
Cell Line
Coronary Vessels
Detergents
Disease Models, Animal
Down-Regulation
Electrophoresis, Gel, Two-Dimensional
Female
Humans
Immunohistochemistry
Immunosuppressive Agents
Kidney
Kidney Diseases
Macaca mulatta
Mass Spectrometry
Muscle, Smooth
Nephritis
Phosphoproteins
Phosphorylation
Reverse Transcriptase Polymerase Chain Reaction
Selenium-Binding Proteins
Transforming Growth Factor beta
Tyrosine
Uterus
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a