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

Sára Kálmán, Krassimira A. Garbett, Andrea Vereczkei, Richard C. Shelton, Z. Korade, K. Mirnics

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)343-353
Number of pages11
JournalExperimental Cell Research
Volume320
Issue number2
DOIs
Publication statusPublished - Jan 15 2014

Fingerprint

Physiological Stress
MicroRNAs
Fibroblasts
Messenger RNA
Galactose
Transcriptome
Physiological Phenomena
Physiological Adaptation
Skin
Genes
Psychiatry
Healthy Volunteers
Oxidative Stress
Homeostasis
Cholesterol
Lipids
Biopsy
Gene Expression
Glucose
Brain

Keywords

  • Galactose
  • Human fibroblast
  • Lipid
  • MiRNA
  • MRNA
  • Profiling
  • QPCR
  • Stress

ASJC Scopus subject areas

  • Cell Biology

Cite this

Metabolic stress-induced microRNA and mRNA expression profiles of human fibroblasts. / Kálmán, Sára; Garbett, Krassimira A.; Vereczkei, Andrea; Shelton, Richard C.; Korade, Z.; Mirnics, K.

In: Experimental Cell Research, Vol. 320, No. 2, 15.01.2014, p. 343-353.

Research output: Contribution to journalArticle

Kálmán, Sára ; Garbett, Krassimira A. ; Vereczkei, Andrea ; Shelton, Richard C. ; Korade, Z. ; Mirnics, K. / Metabolic stress-induced microRNA and mRNA expression profiles of human fibroblasts. In: Experimental Cell Research. 2014 ; Vol. 320, No. 2. pp. 343-353.
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