Prevention of chronic renal allograft rejection by SERP-1 protein

Eric L.R. Bédard, Jifu Jiang, Jacqueline Arp, Hua Qian, Hao Wang, Haiyan Guan, Liying Liu, Neil Parry, Peter Kim, Bertha Garcia, Xing Li, Colin Macaulay, Grant McFadden, Alexandra Lucas, Robert Zhong

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background. In previous studies we have demonstrated that Serp-1, a myxoma virus encoded serine protease inhibitor, dramatically inhibits neointimal hyperplasia in vascular injury and aortic transplant models. Here we examined the effect of peritransplant Serp-1 administration on chronic renal allograft rejection. Methods. Rat renal transplants were performed with sequential recipient sacrifice on postoperative days 2, 10 and 140 to examine both the acute and chronic effects of Serp-1 in recipient rats. Results. Serp-1 administration reduced early posttransplant injury (POD 2) with less acute tubular and vascular necrosis. This translated into a reduction of the characteristic late stage changes of chronic rejection (POD 140), with significantly decreased glomerulosclerosis and neointimal hyperplasia. Effects of Serp-1 treatment were already evident as early as POD 2 with markedly decreased levels of TGF-β mRNA witnessed at both the early and late time points (POD 2, 10 and 140). Conclusion. We have demonstrated that peritransplant Serp-1 viral protein decreased early injury and allowed reduced chronic rejection in a rat renal model. Recipients treated with Serp-1 are associated with a decrease in TGF-β mRNA levels in the allografts suggesting that the serine protease inhibitor may inhibit TGF-β transcription and its profibrotic effects.

Original languageEnglish (US)
Pages (from-to)908-914
Number of pages7
JournalTransplantation
Volume81
Issue number6
DOIs
StatePublished - Mar 2006
Externally publishedYes

Keywords

  • Chronic
  • Kidney
  • Rat
  • Rejection
  • SERP-1

ASJC Scopus subject areas

  • Transplantation

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