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

Jose R. Torrealba, Matthew Colburn, Susan Golner, Zhen Chang, Tara Scheunemann, John H. Fechner, Drew Roenneburg, Huaizhong Hu, Tausif Alam, Hyoung T. Kim, Turan Kanmaz, Terry Oberley, Stuart J. Knechtle, Majed M. Hamawy

Research output: Contribution to journalArticle

14 Scopus citations

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 languageEnglish (US)
Pages (from-to)58-67
Number of pages10
JournalAmerican Journal of Transplantation
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2005

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Keywords

  • Atherosclerosis
  • Chronic allograft nephropathy
  • Selenium-binding protein-1
  • Smooth muscle
  • Transplantation
  • Vascular rejection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Torrealba, J. R., Colburn, M., Golner, S., Chang, Z., Scheunemann, T., Fechner, J. H., Roenneburg, D., Hu, H., Alam, T., Kim, H. T., Kanmaz, T., Oberley, T., Knechtle, S. J., & Hamawy, M. M. (2005). Selenium-binding protein-1 in smooth muscle cells is downregulated in a rhesus monkey model of chronic allograft nephropathy. American Journal of Transplantation, 5(1), 58-67. https://doi.org/10.1111/j.1600-6143.2004.00651.x