暴露于氢醌的骨髓间充质干细胞中，组蛋白甲基转移酶 Suv39h1 和 Wnt/β-catenin 信号通路之间的相互调节促进细胞增殖并抑制细胞凋亡。
Mutual regulation between histone methyltransferase Suv39h1 and the Wnt/β-catenin signaling pathway promoted cell proliferation and inhibited apoptosis in bone marrow mesenchymal stem cells exposed to hydroquinone.
发表日期：2024 Aug 21
作者：
Tao Xu, Yilin Shen, Runmin Guo, Chiheng Luo, Yibo Niu, Zhilong Luo, Zhongxin Zhu, Zehui Wu, Xinyu Zhao, Hao Luo, Yuting Gao
来源：
TOXICOLOGY
摘要：
对苯二酚 (HQ) 是苯的代谢产物，在体外研究中经常被用作苯的替代物，并且与急性髓性白血病 (AML) 的发展有关。在苯和HQ引起的血液毒性中，细胞凋亡起着关键作用。然而，HQ 背后的分子机制尚不清楚。研究表明Suv39h1通过调节组蛋白H3K9me3参与调节细胞分裂和增殖。同时，Wnt/β-catenin信号通路在细胞增殖和凋亡中也发挥着重要作用。因此，本研究旨在探讨Suv39h1和Wnt/β-catenin信号通路在HQ对骨髓间充质干细胞（BMSCs）作用中的调节作用，以及对细胞增殖和凋亡的影响。结果表明，HQ 提高了 Suv39h1 和 H3K9me3 的水平，并通过上调 β-catenin、Wnt2b、C-myc 和 Cyclin D1 以及下调 Wnt5a 来激活 Wnt/β-catenin 信号通路，从而导致细胞生长增加和细胞增殖。细胞凋亡减少。 Suv39h1 敲除抑制 Wnt/β-catenin 信号通路。同时，抑制Wnt/β-catenin信号通路导致BMSCs中Suv39h1和H3K9me3的下调。 HQ对BMSCs的作用均通过下调Cyt-C、Bax、Caspase 3和Caspase 9的表达以及上调Bcl-xl的表达来促进细胞增殖并抑制细胞凋亡。因此，我们得出结论，Suv39h1和Wnt/β-catenin信号通路可能在HQ对BMSCs的影响中相互调节，从而改善BMSCs的功能改变。版权所有©2024 Elsevier B.V.保留所有权利。
Hydroquinone (HQ), a metabolite of benzene, is frequently utilized as a surrogate for benzene in in vitro studies and is associated with the development of acute myeloid leukemia (AML). In the hemotoxicity caused by benzene and HQ, cell apoptosis plays a key role. However, the molecular mechanisms underlying HQ are unknown. Studies have indicated that Suv39h1 is involved in regulating cell division and proliferation by regulating histone H3K9me3. Meanwhile, the Wnt/β-catenin signaling pathway also plays a significant role in cell proliferation and apoptosis. Therefore, this study was aimed at exploring the regulatory role of Suv39h1 and the Wnt/β-catenin signaling pathway in the effects of HQ on bone marrow mesenchymal stem cells (BMSCs), as well as its influence on cell proliferation and apoptosis. The results demonstrated that HQ elevated the levels of Suv39h1 and H3K9me3 and activated the Wnt/β-catenin signaling pathway by upregulating β-catenin, Wnt2b, C-myc, and Cyclin D1 and downregulating Wnt5a, resulting in an increase in cell growth and a decrease in apoptosis. Suv39h1 knockdown inhibited the Wnt/β-catenin signaling pathway. Meanwhile, inhibition of the Wnt/β-catenin signaling pathway resulted in the down-regulation of Suv39h1 and H3K9me3 in BMSCs. They both promoted cell proliferation and inhibited apoptosis in the effects of HQ on BMSCs by downregulating the expression of Cyt-C, Bax, Caspase 3, and Caspase 9 and upregulating the expression of Bcl-xl. Therefore, we concluded that Suv39h1 and the Wnt/β-catenin signaling pathway may mutually regulate each other in the effects of HQ on BMSCs in order to ameliorate the altered function of BMSCs.Copyright © 2024 Elsevier B.V. All rights reserved.