β-catenin signaling inhibitors ICG-001 and C-82 improve fibrosis in preclinical models of endometriosis
β-catenin signaling inhibitors ICG-001 and C-82 improve fibrosis in preclinical models of endometriosis
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DOI：
10.1038/s41598-019-56302-4
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发表时间：
2019-12-27
影响因子：
4.6
通讯作者：
Narahara, Hisashi
中科院分区：
文献类型：
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作者：
Hirakawa, Tomoko;Nasu, Kaei;Narahara, Hisashi
子宫内膜异位症表现出独特的特征，如纤维化、抗凋亡、促进细胞增殖等；然而，其病理生理学尚未完全了解。治疗后复发率高，进展风险持续至绝经期；因此，需要更有效的子宫内膜异位症治疗方法。 CREB 结合蛋白 (CBP)/β-连环蛋白信号传导抑制剂已在肝、肺和皮肤疾病中表现出抗纤维形成作用。本研究使用来自卵巢的子宫内膜异位囊肿基质细胞和来自子宫的正常子宫内膜基质细胞评估了两种CBP/β-连环蛋白信号抑制剂ICG-001和C-82对子宫内膜异位症进展的影响。 ICG-001 也在小鼠模型中进行了评估。 ICG-001 和 C-82 抑制细胞增殖、纤维形成和细胞迁移，并在体外促进细胞凋亡。 ICG-001 抑制小鼠模型中子宫内膜异位病变的生长。 CBP/β-连环蛋白信号在子宫内膜异位症的病理生理学中发挥重要作用。抑制 CBP/β-连环蛋白信号可以成为子宫内膜异位症的治疗靶点。
Endometriosis exhibits unique characteristics, such as fibrosis, resistance to apoptosis, and promotion of cell proliferation; however, its pathophysiology is not fully understood. Recurrence rates after treatment are high, and the progression risk continues until menopause; hence, more effective therapy for endometriosis is needed. CREB-binding protein (CBP)/beta-catenin signaling inhibitors have demonstrated antifibrogenetic effects in liver, lung, and skin diseases. The present study evaluated the effects of two CBP/beta-catenin signaling inhibitors, ICG-001 and C-82, on the progression of endometriosis using endometriotic cyst stromal cells from the ovary and normal endo'metrial stromal cells from the uterus. ICG-001 was also evaluated in a mouse model. ICG-001 and C-82 inhibited cell proliferation, fibrogenesis, and cell migration, and promoted apoptosis in vitro. ICG-001 inhibited the growth of endometriotic lesions in the mouse model. CBP/beta-catenin signaling plays an important role in the pathophysiology of endometriosis. Inhibiting the CBP/beta-catenin signal can be a therapeutic target for endometriosis.