McLaughlin Jessica E, Santos Marlen Tellez, Binkley Peter A, Sultana Mubeen, Tekmal Rajeshwar R, Schenken Robert S, Knudtson Jennifer F
Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, MC 7836, San Antonio, TX, 78229, USA.
Reprod Sci. 2020 Apr;27(4):1058-1063. doi: 10.1007/s43032-019-00100-w. Epub 2020 Feb 3.
To characterize the effects of 4-methylumbelliferone (4-MU) on expression of the hyaluronic acid (HA) system and on attachment, migration, and invasion of endometrial epithelial (EECs) and stroma cells (ESCs) to peritoneal mesothelial cells (PMCs), this in vitro study was performed in an Academic Center. De-identified endometrial tissue samples used were from reproductive-aged women. EECs and ESCs isolated from menstrual endometrial biopsies were treated with 4-MU or vehicle. Real-time polymerase chain reaction and western blot were used to assess expression of HA synthases (HAS), hyaluronidase, and standard CD44. Established in vitro assays were used to assess attachment, migration, and invasion with and without treatment with 4-MU. Chi square and Student's t-test were used to analyze the results as appropriate. The addition of 4-MU decreased mRNA and protein expression of HAS 2, HAS 3, and CD44 in EECs and ESCs compared to control. Treatment with 4-MU also decreased attachment, migration, and invasion of EECs and ESCs to PMCs compared to control. 4-MU decreases endometrial cell adhesion, migration, and invasion to PMCs. This effect appears to be mediated by a decrease in HAS 2, HAS 3, and CD44. 4-MU is a potential treatment for endometriosis. Future in vivo studies are needed to evaluate 4-MU as a therapeutic agent for endometriosis.
为了描述4-甲基伞形酮（4-MU）对透明质酸（HA）系统表达以及子宫内膜上皮细胞（EECs）和基质细胞（ESCs）与腹膜间皮细胞（PMCs）的黏附、迁移和侵袭的影响，本体外研究在一个学术中心进行。所使用的经过身份识别去除的子宫内膜组织样本来自育龄妇女。从月经子宫内膜活检中分离出的EECs和ESCs用4-MU或赋形剂处理。采用实时聚合酶链反应和蛋白质印迹法评估透明质酸合成酶（HAS）、透明质酸酶和标准CD44的表达。使用既定的体外试验评估在有无4-MU处理情况下的黏附、迁移和侵袭情况。根据情况使用卡方检验和学生t检验分析结果。与对照组相比，添加4-MU可降低EECs和ESCs中HAS 2、HAS 3和CD44的mRNA和蛋白质表达。与对照组相比，用4-MU处理还可降低EECs和ESCs与PMCs的黏附、迁移和侵袭。4-MU可降低子宫内膜细胞与PMCs的黏附、迁移和侵袭。这种作用似乎是由HAS 2、HAS 3和CD44的减少介导的。4-MU是子宫内膜异位症的一种潜在治疗方法。未来需要进行体内研究以评估4-MU作为子宫内膜异位症治疗药物的效果。
