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Journal of Transplantation
Volume 2012, Article ID 723614, 15 pages
http://dx.doi.org/10.1155/2012/723614
Research Article

Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted Pancreatic Islets

1Diabetes Research Institute, University of Miami, Miami, FL, USA
2Center for Computational Science, University of Miami, Miami, FL, USA
3DeWitt Daughtry Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
4Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
5Institute of Hepatopancreatic Surgery, Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Policlinico San Matteo, Pavia, Italy
6Department of Surgical Sciences, University of Pavia, Pavia, Italy
7Department of Microbiology and Immunology, and Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
8Department of Biomedical Engineering, University of Miami, Miami, FL, USA

Received 14 December 2011; Revised 9 February 2012; Accepted 20 February 2012

Academic Editor: Diego Cantarovich

Copyright © 2012 Valia Bravo-Egana et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nonspecific inflammation in the transplant microenvironment results in β-cell dysfunction and death influencing negatively graft outcome. MicroRNA (miRNA) expression and gene target regulation in transplanted islets are not yet well characterized. We evaluated the impact of inflammation on miRNA expression in transplanted rat islets. Islets exposed in vitro to proinflammatory cytokines and explanted syngeneic islet grafts were evaluated by miRNA arrays. A subset of 26 islet miRNAs was affected by inflammation both in vivo and in vitro. Induction of miRNAs was dependent on NF-κB, a pathway linked with cytokine-mediated islet cell death. RT-PCR confirmed expression of 8 miRNAs. The association between these miRNAs and mRNA target-predicting algorithms in genome-wide RNA studies of β-cell inflammation identified 238 potential miRNA gene targets. Several genes were ontologically associated with regulation of insulin signaling and secretion, diabetes, and islet physiology. One of the most activated miRNAs was miR-21. Overexpression of miR-21 in insulin-secreting MIN6 cells downregulated endogenous expression of the tumor suppressor Pdcd4 and of Pclo, a Ca2+ sensor protein involved in insulin secretion. Bioinformatics identified both as potential targets. The integrated analysis of miRNA and mRNA expression profiles revealed potential targets that may identify molecular targets for therapeutic interventions.