Lambert Elise, Dassé Emilie, Haye Bernard, Petitfrère Emmanuelle
Laboratoire de Biochimie, CNRS FRE 2534, UFR Sciences Exactes et Naturelles de Reims, IFR 53, Moulin de la Housse, BP1039, 51687 Reims Cedex 2, France.
Crit Rev Oncol Hematol. 2004 Mar;49(3):187-98. doi: 10.1016/j.critrevonc.2003.09.008.
Tissue inhibitors of metalloproteinases (TIMPs) are natural inhibitors of matrix metalloproteinases (MMPs) found in most tissues and body fluids. By inhibiting MMPs activities, they participate in tissue remodeling of the extracellular matrix (ECM). The balance between MMPs and TIMPs activities is involved in both normal and pathological events such as wound healing, tissue remodeling, angiogenesis, invasion, tumorigenesis and metastasis. The intracellular signalling controlling both TIMPs and MMPs expression begins to be elucidated and gaining insights into the molecular mechanisms regulated by TIMPs and MMPs could represent a new approach in the development of potential therapeutics. Numerous investigations have pointed out that TIMPs exhibit multifunctional activities distinct from MMP inhibition. In this review, we detailed the multiple activities of TIMPs in vivo and in vitro and we reported their implication in physiological and pathological processes. Further, we documented recent studies of their role in hematopoiesis and we itemized the different signalling pathways they induced.
金属蛋白酶组织抑制剂（TIMPs）是在大多数组织和体液中发现的基质金属蛋白酶（MMPs）的天然抑制剂。通过抑制MMPs的活性，它们参与细胞外基质（ECM）的组织重塑。MMPs和TIMPs活性之间的平衡涉及正常和病理事件，如伤口愈合、组织重塑、血管生成、侵袭、肿瘤发生和转移。控制TIMPs和MMPs表达的细胞内信号传导开始得到阐明，深入了解由TIMPs和MMPs调节的分子机制可能代表了开发潜在治疗方法的新途径。大量研究指出，TIMPs表现出不同于MMP抑制的多功能活性。在这篇综述中，我们详细阐述了TIMPs在体内和体外的多种活性，并报告了它们在生理和病理过程中的作用。此外，我们记录了它们在造血作用中作用的最新研究，并列举了它们诱导的不同信号通路。
