Pharmacology Laboratory of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China.
Hebei TCM Formula Granule Technology Innovation Center, Shijiazhuang, 050091, China.
Reprod Sci. 2022 Aug;29(8):2152-2164. doi: 10.1007/s43032-021-00831-9. Epub 2022 Feb 14.
Endometriosis is a disease that involves dysfunction of mitochondria, imbalance of proliferation, and apoptosis. Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is a major mitochondrial protein which could regulate the mitochondrial function and apoptosis in various tumor cells, promote migration and then lead to tumor progression. This study aimed to explore the role of CHCHD2 on endometriosis. We investigated the expression of CHCHD2 in ectopic and eutopic endometrium tissues of patients with endometriosis and normal endometrium tissues. Furthermore, CHCHD2 was downregulated to explore the corresponding change of mitochondrial function and morphology, mitochondrial-mediated apoptosis pathway, and proliferation and migration of ectopic endometrial stromal cells. Our results demonstrated that the mRNA and protein expression levels of CHCHD2 were significantly increased in eutopic and ectopic endometrium tissues compared with the normal endometrium tissues. The knockdown of CHCHD2 could cause mitochondrial dysfunction, including the opening of mitochondrial permeability transition pore, loss of mitochondrial membrane potential and the release of cytochrome c, and morphological damage. In addition, CHCHD2 down-expression could also lead to inhibition of cell proliferation, decrease of migration ability, and aggravation of mitochondrial-mediated apoptosis. Together, these findings suggest that increased expression of CHCHD2 in endometriotic tissues may contribute to the pathogenesis of endometriosis via regulating mitochondrial function and apoptosis, and CHCHD2 may be a potential target for interrupting the development of endometriosis.
子宫内膜异位症是一种涉及线粒体功能障碍、增殖失衡和细胞凋亡的疾病。卷曲螺旋-环-卷曲螺旋-环结构域蛋白 2（CHCHD2）是一种主要的线粒体蛋白，可调节各种肿瘤细胞的线粒体功能和细胞凋亡，促进迁移，进而导致肿瘤进展。本研究旨在探讨 CHCHD2 在子宫内膜异位症中的作用。我们研究了子宫内膜异位症患者的异位和在位子宫内膜组织以及正常子宫内膜组织中 CHCHD2 的表达。此外，下调 CHCHD2 以探讨相应的线粒体功能和形态变化、线粒体介导的凋亡途径以及异位子宫内膜基质细胞的增殖和迁移。我们的结果表明，与正常子宫内膜组织相比，CHCHD2 的 mRNA 和蛋白表达水平在在位和异位子宫内膜组织中均显著增加。CHCHD2 的敲低可导致线粒体功能障碍，包括线粒体通透性转换孔的开放、线粒体膜电位的丧失和细胞色素 c 的释放以及形态损伤。此外，CHCHD2 下调还可导致细胞增殖抑制、迁移能力下降和线粒体介导的凋亡加重。总之，这些发现表明，CHCHD2 在子宫内膜异位症组织中的高表达可能通过调节线粒体功能和细胞凋亡参与子宫内膜异位症的发病机制，CHCHD2 可能是中断子宫内膜异位症发展的潜在靶点。
