基质金属蛋白酶-1的研究进展

Progress in the studies of matrix metalloproteinase-1

基质金属蛋白酶(MMP)是一类由Zn2+依赖性的内肽酶组成的酶家族,降解细胞外基质成分(ECM)。MMP-1是最先完成蛋白纯化和cDNA克隆的脊椎动物胶原酶,以酶原形式合成,通过蛋白水解作用裂解酶原N-端残基,与其他MMP分享一个催化区及一个序列相似于血红素蛋白的羧端。MMP-1是一个多功能分子,不仅参与细胞外间隙胶原纤维的代谢,也参与许多非基质底物和细胞表面分子的分裂。大量证据指出,MMP-1在不同生理、病理进程中起重要作用,如发育、组织形态建成、创伤修复,并与人类多种疾病有关,包括动脉粥样硬化、风湿性关节炎、肺气肿和纤维化等,提示抑制或刺激MMP-1可有助于疾病预防与治疗。

Matrix metalloproteinases （MMP） are a family of Zn^2 ＋ -dependent endopeptidases capable of cleaving components of extracellular matrix （ECM）. MMP-1 was the first vertebrate collagenase purified as a protein and cloned as a cDNA, and is considered the prototype for all the interstitial collagenases. It is synthesized as a zymogen. Its N-terminal residues are removed by proteolysis and it shares with other MMPs a catalytic domain and a carboxy terminal domain with the sequence similar to hemopexin. MMP-1 should be considered as a muhifunctional molecule since it participates not only in the turnover of collagen fibrils in the extracellular space but also in the cleavage of a number of nonmatrix substrates and cell surface molecules, suggesting an important role in the regulation of cellular behaviour. Furthermore, an extensive body of evidence indicates that MMP-1 plays an important role in diverse physiologic processes such as growth, tissue morphogenesis, and wound repair. Likewise, it seems to be implicated in a variety of human diseases including atherosclerosis, rheumatoid arthritis, pulmonary emphysema, and fibrotie disorders, suggesting that its inhibition or stimulation may open therapeutic avenues.