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 α-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-β blocked the expression of SBP-1; thus, TGF-β 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-β on SMC and in the process of CAN.
Original language | English (US) |
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Pages (from-to) | 58-67 |
Number of pages | 10 |
Journal | American Journal of Transplantation |
Volume | 5 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2005 |
Keywords
- Atherosclerosis
- Chronic allograft nephropathy
- Selenium-binding protein-1
- Smooth muscle
- Transplantation
- Vascular rejection
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)