Hornebeck William, Emonard Hervé, Maquart François-Xavier, Bellon Georges
FRE 2534 CNRS-IFR 53 Biomolécules, Faculté de Médecine, 51 rue Cognacq Jay, 51095 Reims, France.
J Soc Biol. 2003;197(1):25-30.
The degradation of extracellular matrix (ECM) during physio-pathological processes involves, essentially, two proteolytic systems: the plasmin (ogen) system and the matrix metalloproteinase (MMP) family. Enzyme activity necessitates the formation of proteolytic cascades acting in the pericellular environment. Several proteins (proteases, integrins, matrix, inhibitors, activators...) participate to enzyme catalysis forming assemblies within specialized plasma membrane structures (invadopodia, caveolae). MMP-mediated ECM degradation leads to the formation of peptides (matricryptins, matrikins) which, in turn, can modulate MMP expression. MMPs (especially gelatinases) can also activate growth factors as pro TGF beta or liberate those factors from matrix sites. Interaction between matrix and gelatinases was shown to influence enzyme activation through several mechanisms. Finally, thrombospondins 1 and 2, matricellular proteins, can regulate gelatinase A by favoring its endocytosis. Those data emphasize the potential interest of certain matrikins or pseudo-matrikins as therapeutic agents to control cell invasion.
在生理病理过程中，细胞外基质（ECM）的降解主要涉及两个蛋白水解系统：纤溶酶（原）系统和基质金属蛋白酶（MMP）家族。酶活性需要在细胞周围环境中形成蛋白水解级联反应。几种蛋白质（蛋白酶、整合素、基质、抑制剂、激活剂等）参与酶催化，在特殊的质膜结构（侵袭伪足、小窝）内形成组装体。MMP介导的ECM降解导致肽（基质隐窝蛋白、基质相关分子）的形成，反过来，这些肽又可以调节MMP的表达。MMP（尤其是明胶酶）还可以激活生长因子，如前体转化生长因子β，或从基质位点释放这些因子。已表明基质与明胶酶之间的相互作用通过多种机制影响酶的激活。最后，血小板反应蛋白1和2（基质细胞蛋白）可以通过促进其胞吞作用来调节明胶酶A。这些数据强调了某些基质相关分子或假基质相关分子作为控制细胞侵袭的治疗剂的潜在价值。
