Cai Linyi, Xiong Xin, Kong Xiangli, Xie Jing
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 People's Republic of China.
Tissue Eng Regen Med. 2017 Jan 17;14(1):15-30. doi: 10.1007/s13770-016-0007-0. eCollection 2017 Feb.
Tissue injury provokes a series of events containing inflammation, new tissue formation and tissue remodeling which are regulated by the spatially and temporally coordinated organization. It is an evolutionarily conserved, multi-cellular, multi-molecular process via complex signalling network. Tissue injury disorders present grievous clinical problems and are likely to increase since they are generally associated with the prevailing diseases such as diabetes, hypertension and obesity. Although these dynamic responses vary not only for the different types of trauma but also for the different organs, a balancing act between the tissue degradation and tissue synthesis is the same. In this process, the degradation of old extracellular matrix (ECM) elements and new ones' synthesis and deposition play an essential role, especially collagens. Lysyl oxidase (LOX) and four lysyl oxidase-like proteins are a group of enzymes capable of catalyzing cross-linking reaction of collagen and elastin, thus initiating the formation of covalent cross-links that insolubilize ECM proteins. In this way, LOX facilitates ECM stabilization through ECM formation, development, maturation and remodeling. This ability determines its potential role in tissue repair and regeneration. In this review, based on the current , animal and human studies which have shown the significant role of the LOXs in tissue repair, e.g., tendon regeneration, ligament healing, cutaneous wound healing, and cartilage remodeling, we focused on the role of the LOXs in inflammation phase, proliferation phase, and tissue remodeling phase of the repair process. By summarizing its healing role, we hope to shed light on the understanding of its potential in tissue repair and provide up to date therapeutic strategies towards related injuries.
组织损伤引发一系列事件,包括炎症、新组织形成和组织重塑,这些过程由空间和时间上协调的组织来调控。它是一个通过复杂信号网络进行的进化上保守的多细胞、多分子过程。组织损伤性疾病带来严重的临床问题,并且可能会增加,因为它们通常与诸如糖尿病、高血压和肥胖症等常见疾病相关。尽管这些动态反应不仅因创伤类型不同而异,也因不同器官而异,但组织降解与组织合成之间的平衡作用是相同的。在这个过程中,旧细胞外基质(ECM)成分的降解以及新成分的合成与沉积起着至关重要的作用,尤其是胶原蛋白。赖氨酰氧化酶(LOX)和四种赖氨酰氧化酶样蛋白是一组能够催化胶原蛋白和弹性蛋白交联反应的酶,从而启动使ECM蛋白不溶解的共价交联的形成。通过这种方式,LOX通过ECM的形成、发育、成熟和重塑促进ECM的稳定。这种能力决定了它在组织修复和再生中的潜在作用。在这篇综述中,基于目前的动物和人体研究,这些研究已表明LOX在组织修复中具有重要作用,例如肌腱再生、韧带愈合、皮肤伤口愈合和软骨重塑,我们重点关注了LOX在修复过程的炎症期、增殖期和组织重塑期的作用。通过总结其愈合作用,我们希望能阐明对其在组织修复中的潜力的理解,并为相关损伤提供最新的治疗策略。