Transcriptional profiling of stress response in cultured porcine islets

C. M.T. Dvorak, M. Hårdstedt, H. Xie, M. Wang, K. K. Papas, B. J. Hering, M. P. Murtaugh, S. C. Fahrenkrug

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Cell-based diabetes therapy may be achieved through xenotransplantation of adult porcine islets, but tissue quality and immunoreactivity barriers need to be overcome. Early identification and exclusion of irreversibly stressed and dying islets may improve transplant outcomes. We used oligonucleotide microarray and quantitative RT-PCR to identify molecular markers of physiological and immunological stress in porcine islets cultured under stress conditions of elevated glucose (16.7 mM), inflammatory cytokine addition (IL-1β, TNF-α, and IFN-γ), or both, for 48 h. Hyperglycemic conditions were associated with increased thioredoxin interacting protein and metabolic process mRNAs, as observed in rodent and primate species. Cytokine treatment increased expression of JAK-STAT pathway components, oxidative stress (transglutaminase 2), and β cell dysfunction genes. Transglutaminase 2 induction is unique to porcine islets. Biomarkers involved in hyperglycemia and islet inflammation may serve as novel targets for improving and monitoring isolated porcine islet function and viability.

Original languageEnglish (US)
Pages (from-to)118-125
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume357
Issue number1
DOIs
StatePublished - May 25 2007

Bibliographical note

Funding Information:
The authors wish to thank Jeffrey Ansite, Thomas Gilmore, Andrew Friberg, Andrea Bauer, and Dr. Hui-Jian Zhang of the Diabetes Institute for porcine islet isolation and culture, Dr. Zheng Jin Tu at the University of Minnesota Supercomputing Institute for computing support, and Mr. Bhupinder Juneja for technical assistance. Financial support was provided by the Eunice L. Dwan Diabetes Research Endowment, Iacocca Foundation, Children with Diabetes Foundation, and the Winston and Maxine Wallin Islet Xenotransplant Fund.

Keywords

  • Cytokines
  • Diabetes
  • Gene expression
  • Islet cells
  • Microarray
  • Swine

Fingerprint

Dive into the research topics of 'Transcriptional profiling of stress response in cultured porcine islets'. Together they form a unique fingerprint.

Cite this