Indoleamine 2,3-dioxygenase inhibition alters the non-coding RNA transcriptome following renal ischemia-reperfusion injury

Todd D. Merchen, Erika I. Boesen, John R. Gardner, Rachel Harbarger, Eiko Kitamura, Andrew Mellor, David M. Pollock, Arina Ghaffari, Robert Podolsky, N. Stanley Nahman

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: Indoleamine 2,3 dioxygenase (IDO) degrades the essential amino acid tryptophan and has been shown to minimize rejection in animal models of renal transplantation. Ischemia-reperfusion injury (IRI) is unavoidable in renal transplantation and correlates with shorter graft survival times. Despite its favorable effects on rejection, there is evidence that IDO may facilitate renal IRI. Differentiating the negative impact of IDO on IRI from its pro-tolerant effects in allograft rejection is of clinical relevance. In these studies we hypothesized that constitutive IDO activity may influence renal genes associated with recovery from IRI, and that IDO inhibition may unmask these effects. Methods: We examined the renal transcriptome in a rat model of IRI with and without IDO inhibition with 1-methyl- d-tryptophan (1-MT), and assessed for alterations in the gene expression signature. Results: These studies demonstrated that during recovery from renal IRI, pre-treatment with 1-MT alleviated alterations in 105 coding sequences associated with IRI, and in turn triggered new changes in 66 non-coding transcripts, the majority of which were represented by small nucleolar RNA. Conclusion: These results suggest a biologic role for non-coding, IDO-dependent genes in regulating the early response to IRI.

Original languageEnglish (US)
Pages (from-to)140-144
Number of pages5
JournalTransplant Immunology
Volume30
Issue number4
DOIs
StatePublished - May 2014

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Keywords

  • Allograft tolerance
  • DNA microarray
  • Ischemic-reperfusion
  • Non-coding RNA transcriptome
  • Transplantation
  • Tryptophan

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation

Cite this

Merchen, T. D., Boesen, E. I., Gardner, J. R., Harbarger, R., Kitamura, E., Mellor, A., Pollock, D. M., Ghaffari, A., Podolsky, R., & Nahman, N. S. (2014). Indoleamine 2,3-dioxygenase inhibition alters the non-coding RNA transcriptome following renal ischemia-reperfusion injury. Transplant Immunology, 30(4), 140-144. https://doi.org/10.1016/j.trim.2014.04.003