Transcriptome and Metabolome Analyses in Exogenous FABP4- and FABP5-Treated Adipose-Derived Stem Cells.
Transcriptome and Metabolome Analyses in Exogenous FABP4- and FABP5-Treated Adipose-Derived Stem Cells.
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DOI：
10.1371/journal.pone.0167825
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Miura T
中科院分区：
文献类型：
--
作者：
Yamamoto T;Furuhashi M;Sugaya T;Oikawa T;Matsumoto M;Funahashi Y;Matsukawa Y;Gotoh M;Miura T
脂肪源性干细胞（Adipose-derived stem cells，ADSC）是存在于脂肪组织中的一种与脂肪细胞相邻的细胞，已被用作再生医学的潜在工具。脂质伴侣，脂肪酸结合蛋白4（FABP 4）和5（FABP 5），在脂肪细胞中大量表达。FABP 4最近已被证明在脂肪分解期间以非经典途径从脂肪细胞分泌，并且可能充当脂肪因子。在此，我们研究了外源性FABP 4和FABP 5在ADSC转录和代谢调控中的作用。FABP 4和FABP 5在ADSC中表达较少。然而，FABP 4和FABP 5在ADSC脂肪细胞分化后被显著诱导，并从分化的脂肪细胞分泌。微阵列数据的分析，包括基因本体富集分析和使用转录因子结合位点搜索的蛋白质-蛋白质相互作用网络的级联分析，表明用FABP 4或FABP 5处理ADSC影响与炎症和代谢反应以及细胞分化过程相关的几种基因。值得注意的是，成肌因子，包括肌细胞增强因子、成肌分化1和肌细胞生成素，通过用FABP 4处理ADSC来调节，表明外源性FABP 4处理与ADSC中的肌生成部分相关。代谢物组学分析表明，用FABP 4和FABP 5处理ADSC相似，但程度不同，促进了脂质的水解和/或摄取，因此伴随着β氧化的增强，糖酵解途径下游的抑制，氨基酸的积累，核酸组分的减少以及还原型和氧化型烟酰胺腺嘌呤二核苷酸磷酸的比率的增加（NADPH/NADP+）（还原能力的指标）和三磷酸腺苷和一磷酸腺苷的比率（ATP/AMP）（能量状态的指标）。总之，从脂肪细胞分泌的FABP 4和FABP 5作为脂肪因子差异地影响脂肪细胞附近的ADSC的转录和代谢调节。再生医学宿主的肥胖状况可能通过暴露FABP 4和FABP 5的平衡来影响ADSC的特性。
Adipose-derived stem cells (ADSC), which exist near adipocytes in adipose tissue, have been used as a potential tool of regenerative medicine. Lipid chaperones, fatty acid-binding protein 4 (FABP4) and 5 (FABP5), are abundantly expressed in adipocytes. FABP4 has recently been shown to be secreted from adipocytes during lipolysis in a non-classical pathway and may act as an adipokine. Here, we investigated the role of exogenous FABP4 and FABP5 in transcriptional and metabolic regulation in ADSC. FABP4 and FABP5 were little expressed in ADSC. However, both FABP4 and FABP5 were significantly induced after adipocyte differentiation of ADSC and were secreted from the differentiated adipocytes. Analysis of microarray data, including gene ontology enrichment analysis and cascade analysis of the protein-protein interaction network using a transcription factor binding site search, demonstrated that treatment of ADSC with FABP4 or FABP5 affected several kinds of genes related to inflammatory and metabolic responses and the process of cell differentiation. Notably, myogenic factors, including myocyte enhancer factors, myogenic differentiation 1 and myogenin, were modulated by treatment of ADSC with FABP4, indicating that exogenous FABP4 treatment is partially associated with myogenesis in ADSC. Metabolome analysis showed that treatment of ADSC with FABP4 and with FABP5 similarly, but differently in extent, promoted hydrolysis and/or uptake of lipids, consequentially together with enhancement of β oxidation, inhibition of downstream of the glycolysis pathway, accumulation of amino acids, reduction of nucleic acid components and increase in the ratio of reduced and oxidized nicotinamide adenine dinucleotide phosphates (NADPH/NADP+), an indicator of reducing power, and the ratio of adenosine triphosphate and adenosine monophosphate (ATP/AMP), an indicator of the energy state, in ADSC. In conclusion, secreted FABP4 and FABP5 from adipocytes as adipokines differentially affect transcriptional and metabolic regulation in ADSC near adipocytes. The adiposity condition in the host of regenerative medicine may affect characteristics of ADSC by exposure of the balance of FABP4 and FABP5.
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血清脂肪酸结合蛋白 4 是终末期肾病心血管事件的预测因子。
影响因子：
3.7
作者：
Furuhashi M;Ishimura S;Ota H;Hayashi M;Nishitani T;Tanaka M;Yoshida H;Shimamoto K;Hotamisligil GS;Miura T
通讯作者：
Miura T
影响因子：
2
作者：
Furuhashi M;Ishimura S;Ota H;Miura T
通讯作者：
Miura T
DOI：
10.4137/cmc.s17067
发表时间：
2014
期刊：
Clinical Medicine Insights. Cardiology
影响因子：
--
作者：
Furuhashi M;Saitoh S;Shimamoto K;Miura T
通讯作者：
Miura T
影响因子：
3.7
作者：
Furuhashi M;Matsumoto M;Hiramitsu S;Omori A;Tanaka M;Moniwa N;Yoshida H;Ishii J;Miura T
通讯作者：
Miura T
FABP4 通过 MAPK 依赖性途径诱导血管平滑肌细胞增殖和迁移。
影响因子：
3.7
作者：
Girona J;Rosales R;Plana N;Saavedra P;Masana L;Vallvé JC
通讯作者：
Vallvé JC