Selenium-binding protein-1 in smooth muscle cells is downregulated in a rhesus monkey model of chronic allograft nephropathy.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • January 2005

Published In

Volume / Issue

  • 5 / 1

Start / End Page

  • 58 - 67

PubMed ID

  • 15636612

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

International Standard Serial Number (ISSN)

  • 1600-6135

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2004.00651.x

Language

  • eng