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Cited by 43Pancreatic function and diabetesMicroRNA in disease regulationDiabetes and associated disorders

Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted Pancreatic Islets

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Bravo-Egana, Valia, Rosero, Samuel, Klein, Dagmar, Jiang, Zhijie, Vargas, Nancy, Tsinoremas, Nicholas, Doni, Marco, Podetta, Michele +4 more·2012·Journal of Transplantation
DOI 10.1155/2012/723614PMC PMC3359768
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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 Ca 2+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.

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Authors
Bravo-Egana, V., Rosero, S., Klein, D., Jiang, Z., Vargas, N., Tsinoremas, N., Doni, M., Podetta, M., Ricordi, C., Molano, R. D., Pileggi, A., & Pastori, R. L.
Affiliations
  • Diabetes Research Institute, University of Miami, Miami, FL, USA
  • University of Miami (US)
Corresponding author
  • Pileggi, Antonello
  • Pastori, Ricardo L.
ORCID
Venue
Journal of Transplantation
Publisher
Wiley
Published
2012
Volume
2012
Pages
1-15
ISSN
  • 2090-0007 (ISSN-L)
  • 2090-0015
DOI
10.1155/2012/723614
PMC
PMC3359768
OpenAlex
W1966219265
Cited by
43
References
3
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 8 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 7 · 2012: 1
FWCI
5.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Transplantation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Diabetes Research Institute Foundation
  • American Diabetes Association
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
microRNA expression, islet transplantation, inflammation, inflammatory cytokines, NF-κB signaling, beta-cell dysfunction, miR-21, PDCD4, PCLO, insulin secretion, insulin signaling, MIN6 cells, islet cell death

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