High-mobility group box 2 protein is essential for the early phase of adipogenesis
High-mobility group box 2 protein is essential for the early phase of adipogenesis
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高迁移率 group box 2 蛋白对于脂肪形成的早期阶段至关重要
DOI：
10.1016/j.bbrc.2021.03.149
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Toshihiko Yanase
中科院分区：
文献类型：
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作者：
Hidetaka Morinaga;Yoshimi Muta;Tomoko Tanaka;Makito Tanabe;Yuriko Hamaguchi;Toshihiko Yanase
了解脂肪形成的机制对于控制肥胖是至关重要的，肥胖易导致许多健康问题。高迁移率族蛋白2（HMGB 2）是一种非组蛋白的染色体蛋白，促进DNA复制，转录，重组和修复。在此，我们研究了HMGB 2在成脂分化中的作用。在培养的3 T3-L1前脂肪细胞中以及在由胰岛素、3-异丁基-1-甲基黄嘌呤和地塞米松的混合物诱导的成脂分化过程中，在mRNA和蛋白水平上测量HMGB 2的表达。这在分化的早期阶段增加，在分化的晚期阶段减少。然而，3 T3-L1前脂肪细胞在通过小干扰RNA（siRNA）敲低HMGB 2表达后没有分化成脂肪细胞。同样，从Hmgb 2 −/−小鼠中分离的间充质干细胞（MSC）在脂肪细胞分化混合物中不表达过氧化物酶体增殖物激活受体γ（PPARγ），也不分化。Wnt/β-catenin信号是脂肪形成分化的负调节因子。我们发现β-catenin的表达在3 T3-L1成脂分化过程中下调，正如预期的那样，但当内源性HMBG 2表达被siRNA敲低时却没有。这些结果表明HMGB 2在前脂肪细胞和MSCs的早期分化中起着重要作用，并可能与其他调节因子如PPARγ和Wnt/β-catenin信号相互作用。
Understanding of the mechanism of adipogenesis is essential for the control of obesity, which predisposes toward numerous health problems. High-mobility group box protein 2 (HMGB2) is a non-histone chromosomal protein that facilitates DNA replication, transcription, recombination, and repair. Here, we studied the role of HMGB2 in adipogenic differentiation. The expression of HMGB2 was measured at the mRNA and protein levels in cultured 3T3-L1 pre-adipocyte cells and during the process of adipogenic differentiation induced bya cocktail of insulin, 3-isobutyl-1-methylxanthine, and dexamethasone. This increased in the early phase and decreased in the late phase of differentiation. However, 3T3-L1 pre-adipocyte cells did not differentiate into adipocytes after the knockdown of HMGB2 expression by small interfering RNA (siRNA). Similarly, mesenchymal stem cells (MSCs) isolated fromHmgb2−/−mice did not express peroxisome proliferator-activated receptor gamma (PPARγ) in response to the adipocyte differentiation cocktail and did not differentiate. Wnt/β-catenin signaling is a negative regulator of adipogenic differentiation. We found that β-catenin expression was downregulated during 3T3-L1 adipogenic differentiation, as expected, but not when endogenous HMBG2 expression was knocked down using siRNA. These results indicate that HMGB2 plays an essential role in the early phase of the differentiation of pre-adipocytes and MSCs, and probably interacts with other regulators, such as PPARγ and Wnt/β-catenin signaling.