MicroRNA-143 regulates adipogenesis by modulating the MAP2K5-ERK5 signaling.
MicroRNA-143 regulates adipogenesis by modulating the MAP2K5-ERK5 signaling.
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DOI：
10.1038/srep03819
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发表时间：
2014-01-22
影响因子：
4.6
通讯作者：
Liu L
中科院分区：
文献类型：
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作者：
Chen L;Hou J;Ye L;Chen Y;Cui J;Tian W;Li C;Liu L
更好地了解脂肪组织来源的基质细胞（ADSC）分化的分子机制，可以为一些脂肪组织相关疾病提供新的见解。脂肪干细胞分化为脂肪细胞是一个复杂的生理过程，包括克隆扩增、生长停滞和终末分化。本文系统研究了microRNA-143（miR-143）在ADSC成脂分化过程中的作用。我们发现miR-143表达在成脂诱导后短暂降低，而从诱导后第3天开始增加，并在诱导后第7天达到峰值。我们首次发现miR-143在分化过程中的作用并不一致。其调控作用取决于miR-143作用的分化阶段，当miR-143在克隆扩增阶段过表达时，ADSCs的成脂分化受到抑制，而在生长停滞阶段或终末分化阶段过表达时，则促进分化。我们还首次证实了miR-143通过直接抑制MAPK信号通路中MAPKK家族的关键成员MAP 2K 5而发挥调控作用。这些发现表明，miR-143在脂肪组织形成中起着重要作用，对于脂肪组织的数量和/或功能改变的一些代谢疾病具有特殊意义。
A better understanding of the molecular mechanisms that regulate adipose tissue-derived stromal cell (ADSC) differentiation could provide new insight into some adipose-tissue-related disease. The differentiation of ADSCs into adipocytes is a complex physiological process that includes clonal expansion, growth arrest, and terminal differentiation. Here the role of microRNA-143 (miR-143) during ADSC adipogenic differentiation was systematically investigated. We found that miR-143 expression was transiently decreased after adipogenic induction while increased from day 3 and peaked on day 7 after induction. We show for the first time that the role of miR-143 is not consistent in the differentiation process. The regulatory role depends on the differentiation stage that miR-143 acts on. When miR-143 is overexpressed during the clonal expansion stage, the adipogenic differentiation of ADSCs is inhibited, whereas the overexpression of miR-143 during the growth arrest stage or terminal differentiation stage promotes differentiation. Further we firstly demonstrate that miR-143 plays the modulational role by directly repressing MAP2K5, a key member of the MAPKK family in the MAPK signaling pathway. These findings suggest that miR-143 plays an important role in adipose tissue formation, with special implications for some metabolic disease in which the amount and/or function of adipose tissue is altered.