Abraham David, Ponticos Markella, Nagase Hideaki
Centre for Rheumatology and Connective Tissue Diseases, Department of Medicine, Royal Free and University College Medical School, London, UK.
Curr Vasc Pharmacol. 2005 Oct;3(4):369-79. doi: 10.2174/157016105774329480.
Connective tissue remodeling is achieved by a complex process involving several cell types, a plethora of growth factors, cytokines, chemokines and turnover of extracellular matrix (ECM). The main enzymes that degrade ECM molecules are matrix metalloproteinases (MMPs) and their activities are regulated by endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Recent studies have indicated that endothelins and their receptor expression affects tissue remodeling and repair. Endothelins are rapidly produced by endothelial cells in response to tissue injury and they have potent vasoconstrictive properties. They also promote tissue remodeling through activation of resident connective tissue cells and controlling the production of MMPs and TIMPs by the activated cells. In this review we present the cross-talk between the endothelins and the MMP-TIMP system and their implications in controlling the normal and abnormal tissue remodeling.
结缔组织重塑是一个复杂的过程，涉及多种细胞类型、大量生长因子、细胞因子、趋化因子以及细胞外基质（ECM）的更新。降解ECM分子的主要酶是基质金属蛋白酶（MMPs），其活性受内源性抑制剂金属蛋白酶组织抑制剂（TIMPs）的调节。最近的研究表明，内皮素及其受体表达会影响组织重塑和修复。内皮细胞在组织损伤时会迅速产生内皮素，它们具有强大的血管收缩特性。它们还通过激活驻留的结缔组织细胞以及控制激活细胞产生MMPs和TIMPs来促进组织重塑。在本综述中，我们阐述了内皮素与MMP-TIMP系统之间的相互作用及其在控制正常和异常组织重塑中的意义。
