赖氨酰氧化酶样 2 失调增加女性生殖道术后纤维化疤痕形成的风险:减少纤维形成的新治疗靶点

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current medicinal chemistry Pub Date : 2024-06-27 DOI:10.2174/0109298673306240240612055116
Rozita Khodashahi, Shirin Dehkordi, Amir Mahmoud Ahmadzade, Gordon A Ferns, Mohsen Aliakbarian, Mohammad-Hassan Arjmand
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引用次数: 0

摘要

女性生殖系统(包括子宫)在腹部和盆腔手术后会形成纤维化带,这是一个重要的医学难题,与许多并发症有关,包括不孕和疼痛。研究参与纤维化和粘连形成的不同分子的作用可能有助于开发预防这种疾病的新药。赖氨酰氧化酶样 2(LoxL2)是一种铜依赖性酶,可催化细胞外基质(ECM)中胶原蛋白和弹性纤维的交联,从而稳定 ECM。女性生殖道妇科手术后组织缺氧和炎症导致的 LoxL2 活性失调会增加胶原纤维交联并促进纤维化。研究表明,以 LoxL2 为靶点的 Lox 抑制剂可减轻纤维化。考虑到 LoxL2 在女性生殖器官中的表达及其在缺氧和炎症中的失调,LoxL2 作为预防粘连的药物靶点可能具有治疗潜力。在这篇综述中,我们讨论了 LoxL2 在促进纤维化过程中的作用,重点是其与炎症和缺氧条件的联系。我们还论证了使用抗 LoxL2 药物作为预防手术后疤痕形成的潜在治疗策略的合理性。
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Lysyl Oxidase-like 2 Dysregulation Increases the Risk of Post-Operative Fibrotic Scars Formation in the Female Reproductive Tract: A Novel Therapeutic Target to Reduce Fibrogenesis.

The formation of fibrotic bands in female reproductive system, including the uterus, after abdominal and pelvic surgeries, is an important medical challenge associated with many complications, including infertility and pain. Investigating the role of different molecules involved in fibrosis and adhesion formation may help in the development of new drugs to prevent this disorder. Lysyl oxidase-like 2 (LoxL2) is a copper-dependent enzyme that catalyzes the cross-linking of collagen and elastin fibers in the extracellular matrix (ECM) to stabilize ECM. Dysregulation of LoxL2 activity resulting from tissue hypoxia and inflammation after gynecological surgeries in the female reproductive tract increases collagen fibers cross-linking and promotes fibrosis. It has been shown that targeting LoxL2 by Lox inhibitors may reduce fibrosis. Considering the expression of LoxL2 in female reproductive organs and its dysregulation in hypoxia and inflammation, it is possible that LoxL2 has therapeutic potential as a drug target in the prevention of adhesions. In this review, we discuss the role of LoxL2 in the promotion of fibrotic processes focusing on its link with inflammatory and hypoxic conditions. We also justify the use of anti- LoxL2 agents as a potential therapeutic strategy for the prevention of post-surgical scar formation.

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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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