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Exp Cell Res. 2014 Jan 15;320(2):343-53. doi: 10.1016/j.yexcr.2013.10.019. Epub 2013 Nov 16.

Metabolic stress-induced microRNA and mRNA expression profiles of human fibroblasts.

Author information

  • 1Department of Psychiatry, University of Szeged, Szeged, Hungary.
  • 2Department of Psychiatry, Vanderbilt University, Nashville, TN, USA.
  • 3Department of Psychiatry, University of Szeged, Szeged, Hungary; Institute for Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
  • 4Department of Psychiatry, University of Alabama, Birmingham, AL, USA.
  • 5Department of Psychiatry, University of Szeged, Szeged, Hungary; Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA.
  • 6Department of Psychiatry, University of Szeged, Szeged, Hungary; Department of Psychiatry, Vanderbilt University, Nashville, TN, USA; Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA. Electronic address: karoly.mirnics@vanderbilt.edu.

Abstract

Metabolic and oxidative stresses induce physiological adaptation processes, disrupting a finely tuned, coordinated network of gene expression. To better understand the interplay between the mRNA and miRNA transcriptomes, we examined how two distinct metabolic stressors alter the expression profile of human dermal fibroblasts. Primary fibroblast cultures were obtained from skin biopsies of 17 healthy subjects. Metabolic stress was evoked by growing subcultured cells in glucose deprived, galactose enriched (GAL) or lipid reduced, cholesterol deficient (RL) media, and compared to parallel-cultured fibroblasts grown in standard (STD) medium. This was followed by mRNA expression profiling and assessment of >1000 miRNAs levels across all three conditions. The miRNA expression levels were subsequently correlated to the mRNA expression profile. Metabolic stress by RL and GAL both produced significant, strongly correlated mRNA/miRNA changes. At the single gene level four miRNAs (miR-129-3p, miR-146b-5p, miR-543 and miR-550a) showed significant and comparable expression changes in both experimental conditions. These miRNAs appeared to have a significant physiological effect on the transcriptome, as nearly 10% of the predicted targets reported changes at mRNA level. The two distinct metabolic stressors induced comparable changes in the miRNome profile, suggesting a common defensive response of the fibroblasts to altered homeostasis. The differentially expressed miR-129-3p, miR-146b-5p, miR-543 and miR-550a regulated multiple genes (e.g. NGEF, NOVA1, PDE5A) with region- and age-specific transcription in the human brain, suggesting that deregulation of these miRNAs might have significant consequences on CNS function. The overall findings suggest that analysis of stress-induced responses of peripheral fibroblasts, obtained from patients with psychiatric disorders is a promising avenue for future research endeavors.

© 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

Galactose; Human fibroblast; Lipid; Profiling; Stress; mRNA; miRNA; qPCR

PMID:
24246224
[PubMed - indexed for MEDLINE]
PMCID:
PMC3902643
Free PMC Article
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