Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway.
Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway.
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DOI：
10.1177/0963689718795692
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发表时间：
2018-10
影响因子：
3.3
通讯作者：
Lerman LO
中科院分区：
文献类型：
--
作者：
Meng Y;Eirin A;Zhu XY;Tang H;Hickson LJ;Lerman A;van Wijnen AJ;Lerman LO
间充质干细胞（MSC）是一种重要的修复系统，但暴露于心血管危险因素可能会受损。因此，来自患有代谢综合征（MetS）的猪的脂肪组织来源的MSC显示出降低的活力。越来越多的microRNA（miRNAs）被认为是衰老的关键调节因子，但它们在调节MetS中MSC衰老中的作用尚不清楚。我们测试了MetS上调MSC中可作为衰老相关（SA）基因转录后调节因子的miRNA表达的假设。在16周的瘦饮食或肥胖饮食后从猪腹部脂肪组织收集MSC（各n = 6）。进行下一代miRNA测序（miRNA-seq）以鉴定与Lean-MSC相比在MetS-MSC中上调或下调的miRNA。利用基因本体论分析了SA基因的功能通路。通过p16和p21免疫反应性、H2 AX蛋白表达和SA-β-半乳糖苷酶活性评价MSC衰老。此外，在抑制SA-miR-27 b后，研究了p16、p21、MAPK 3（ERK 1）和MAPK 14的基因表达以及MSC迁移。衰老生物标志物在MetS-MSC中显著升高。我们在MetS-MSCs中发现了7个上调的miRNA，包括miR-27 b，和3个下调的miRNA，它们调节35个SA基因，特别是MAPK信号。在培养的MSC中抑制miR-27 b下调p16和MARP 3基因，并增加MSC迁移。MetS调节MSC的SA-miRNA表达，这可能调节其衰老，而p16途径似乎在MetS诱导的MSC衰老中发挥重要作用。
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-β-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.
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影响因子：
3.3
作者：
Eirin A;Zhu XY;Ebrahimi B;Krier JD;Riester SM;van Wijnen AJ;Lerman A;Lerman LO
通讯作者：
Lerman LO
影响因子：
2.7
作者：
Cao, Zhenguo;Chen, Liang
通讯作者：
Chen, Liang
影响因子：
3.3
作者：
Ahn, So Yoon;Chang, Yun Sil;Park, Won Soon
通讯作者：
Park, Won Soon
影响因子：
18.2
作者：
Campisi J
通讯作者：
Campisi J
DOI：
10.1016/j.bbalip.2016.02.010
发表时间：
2016-12
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Price NL;Fernández-Hernando C
通讯作者：
Fernández-Hernando C