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关于细胞外基质在子宫肌瘤发病机制中的作用和调控机制的最新研究进展。

Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids.

机构信息

Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA.

出版信息

Int J Mol Sci. 2023 Mar 17;24(6):5778. doi: 10.3390/ijms24065778.

Abstract

Uterine fibroids (UFs), also known as leiomyomas, are benign tumors of the myometrium affecting over 70% of women worldwide, particularly women of color. Although benign, UFs are associated with significant morbidity; they are the primary indication for hysterectomy and a major source of gynecologic and reproductive dysfunction, ranging from menorrhagia and pelvic pain to infertility, recurrent miscarriage, and preterm labor. So far, the molecular mechanisms underlying the pathogenesis of UFs are still quite limited. A knowledge gap needs to be filled to help develop novel strategies that will ultimately facilitate the development of therapies and improve UF patient outcomes. Excessive ECM accumulation and aberrant remodeling are crucial for fibrotic diseases and excessive ECM deposition is the central characteristics of UFs. This review summarizes the recent progress of ascertaining the biological functions and regulatory mechanisms in UFs, from the perspective of factors regulating ECM production, ECM-mediated signaling, and pharmacological drugs targeting ECM accumulation. In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of the extracellular matrix in the pathogenesis of UFs and in applications. Comprehensive and deeper insights into ECM-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with this common tumor.

摘要

子宫肌瘤(UFs),又称平滑肌瘤,是一种影响全球超过 70%的女性、尤其是有色人种女性的良性子宫平滑肌肿瘤。尽管是良性的,但 UFs 与显著的发病率相关;它们是子宫切除术的主要指征,也是妇科和生殖功能障碍的主要原因,包括月经过多和盆腔疼痛、不孕、复发性流产和早产。到目前为止,UFs 发病机制的分子机制仍然相当有限。需要填补知识空白,以帮助制定新的策略,最终促进治疗方法的发展并改善 UF 患者的预后。细胞外基质(ECM)的过度积累和异常重塑对于纤维化疾病至关重要,而 ECM 的过度沉积是 UFs 的中心特征。本综述从调节 ECM 产生的因素、ECM 介导的信号以及针对 ECM 积累的药物等方面,总结了最近在 UFs 中确定生物学功能和调控机制的进展。此外,我们通过讨论细胞外基质在 UFs 发病机制中的调节作用和新兴作用以及在应用中的作用,提供了目前的知识状态。深入了解 ECM 介导的改变和细胞事件中的相互作用将有助于开发治疗这种常见肿瘤的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e465/10051203/08949f45ad05/ijms-24-05778-g001.jpg

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