Khodashahi Rozita, Dehkordi Shirin Moazen, Ahmadzade Amir Mahmoud, Ferns Gordon A, Aliakbarian Mohsen, Arjmand Mohammad-Hassan
Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Clinical Research Development Unit, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Curr Med Chem. 2025;32(26):5518-5529. doi: 10.2174/0109298673306240240612055116.
The formation of fibrotic bands in the 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, LoxL2 may have theraputic 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.
腹部和盆腔手术后,女性生殖系统(包括子宫)中纤维化带的形成是一个重要的医学挑战,它与许多并发症相关,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)是一种依赖铜的酶,它催化细胞外基质(ECM)中胶原蛋白和弹性蛋白纤维的交联,以稳定ECM。女性生殖道妇科手术后,组织缺氧和炎症导致LoxL2活性失调,增加了胶原纤维交联并促进纤维化。研究表明,用Lox抑制剂靶向LoxL2可能会减少纤维化。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,重点关注其与炎症和缺氧状态的联系。我们还论证了使用抗LoxL2药物作为预防术后瘢痕形成的潜在治疗策略的合理性。