Dataset Information

Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway.

ABSTRACT: Mesenchymal stem cells (MSCs) constitute an important repair system, but may be impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue-derived MSCs from pigs with the metabolic syndrome (MetS) show decreased vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators of senescence, but their role in regulating senescence in MSC in MetS is unclear. We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that can serve as post-transcriptional regulators of senescence-associated (SA) genes. MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet ( n = 6 each). Next-generation miRNA sequencing (miRNA-seq) was performed to identify miRNAs up-or down-regulated in MetS-MSCs compared with Lean-MSCs. Functional pathways of SA genes targeted by miRNAs were analyzed using gene ontology. MSC senescence was evaluated by p16 and p21 immunoreactivity, H2AX protein expression, and SA-?-Galactosidase activity. In addition, gene expression of p16, p21, MAPK3 (ERK1) and MAPK14, and MSC migration were studied after inhibition of SA-miR-27b. Senescence biomarkers were significantly elevated in MetS-MSCs. We found seven upregulated miRNAs, including miR-27b, and three downregulated miRNAs in MetS-MSCs, which regulate 35 SA genes, particularly MAPK signaling. Inhibition of miR-27b in cultured MSCs downregulated p16 and MARP3 genes, and increased MSC migration. MetS modulates MSC expression of SA-miRNAs that may regulate their senescence, and the p16 pathway seems to play an important role in MetS-induced MSC senescence.

SUBMITTER: Meng Y

PROVIDER: S-EPMC6180720 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway.

Meng Y Y Eirin A A Zhu X-Y XY Tang H H Hickson L J LJ Lerman A A van Wijnen A J AJ Lerman L O LO

Cell transplantation 20180906 10

Mesenchymal stem cells (MSCs) constitute an important repair system, but may be impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue-derived MSCs from pigs with the metabolic syndrome (MetS) show decreased vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators of senescence, but their role in regulating senescence in MSC in MetS is unclear. We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that can serve as post-tra ...[more]

PMID: 30187775

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Project description:Introduction: Epicardial adipose tissue (EAT) has been linked to incidence and recurrence of atrial fibrillation (AF), but the underlying mechanisms that mediate this association remain unclear. Circulating microRNAs (miRNAs) contribute to the regulation of gene expression in cardiovascular diseases, including AF. Thus, we sought to test the hypothesis that circulating miRNAs relate to burden of EAT. Methods: We examined the plasma miRNA profiles of 91 participants from the miRhythm study, an ongoing study examining associations between miRNA and AF. We quantified plasma expression of 86 unique miRNAs commonly expressed in cardiomyocytes using quantitative reverse transcriptase polymerase chain reaction (qPCR). From computed tomography, we used validated methods to quantify the EAT area surrounding the left atrium (LA) and indexed it to body surface area (BSA) to calculate indexed LA EAT (iLAEAT). Participants were divided into tertiles of iLAEAT to identify associations with unique miRNAs. We performed logistic regression analyses adjusting for factors associated with AF to examine relations between iLAEAT and miRNA. We performed further bioinformatics analysis of miRNA predicted target genes to identify potential molecular pathways are regulated by the miRNAs. Results: The mean age of the participants was 59 ± 9, 35% were women, and 97% were Caucasian. Participants in the highest tertile of iLAEAT were more likely to have hypertension, heart failure, and thick posterior walls. In regression analyses, we found that miRNAs 155-5p (p < 0.001) and 302a-3p (p < 0.001) were significantly associated with iLAEAT in patients with AF. The predicted targets of the miRNAs identified were implicated in the regulation of cardiac hypertrophy, adipogenesis, interleukin-8 (IL-8), and nerve growth factor (NGF) signaling. Conclusion: miRNA as well as EAT have previously been linked to AF. Our finding that iLAEAT and miRNAs 155-5p and 302a-3p are associated suggest a possible direct link to between these entities in the development and maintenance of AF. Further research is needed to study causal relationships between these biomarkers.

Dataset Information

Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway.

Publications

Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway.

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