Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States.
Department of Anesthesiology and CCM, Johns Hopkins University, Baltimore, Maryland, United States.
Am J Physiol Cell Physiol. 2023 Sep 1;325(3):C694-C707. doi: 10.1152/ajpcell.00176.2023. Epub 2023 Jul 17.
Fibrosis is an important and essential reparative response to injury that, if left uncontrolled, results in the excessive synthesis, deposition, remodeling, and stiffening of the extracellular matrix, which is deleterious to organ function. Thus, the sustained activation of enzymes that catalyze matrix remodeling and cross linking is a fundamental step in the pathology of fibrotic diseases. Recent studies have implicated the amine oxidase lysyl oxidase like-2 (LOXL2) in this process and established significantly elevated expression of LOXL2 as a key component of profibrotic conditions in several organ systems. Understanding the relationship between LOXL2 and fibrosis as well as the mechanisms behind these relationships can offer significant insights for developing novel therapies. Here, we summarize the key findings that demonstrate the link between LOXL2 and fibrosis and inflammation, examine current therapeutics targeting LOXL2 for the treatment of fibrosis, and discuss future directions for experiments and biomedical engineering.
纤维化是一种重要且必需的组织修复反应,如果不受控制,会导致细胞外基质过度合成、沉积、重塑和变硬,从而对器官功能造成损害。因此,持续激活催化基质重塑和交联的酶是纤维化疾病病理学的一个基本步骤。最近的研究表明,胺氧化酶赖氨酰氧化酶样-2(LOXL2)参与了这一过程,并确定 LOXL2 的显著高表达是几种器官系统中致纤维化条件的关键组成部分。了解 LOXL2 与纤维化以及这些关系背后的机制之间的关系,可以为开发新的治疗方法提供重要的见解。在这里,我们总结了表明 LOXL2 与纤维化和炎症之间存在联系的关键发现,检查了目前针对 LOXL2 治疗纤维化的治疗方法,并讨论了实验和生物医学工程的未来方向。