Fragmentation of fibronectin by inherent autolytic and matrix metalloproteinase activities

摘要: Fibronectin (FN) purified by gelatin affinity chromatography is unstable and undergoes fragmentation. The cleavage has been ascribed to inherent autolytic protease activities as well co-purified matrix metalloproteinases (MMP). Understanding the mechanism which proteolysis of FN occurs important, because fragments have biological that differ from those intact FN. Having excluded contributions other plasma-derived proteases, present experiments demonstrated MMP-2 distinct occurred in synergy with activities. Limited heat treatment at 56 °C for 30 min inactivated sharply reducing autolysis a manner similar seen presence serine proteinase inhibitors. Heat did not alter cell attachment FN, but significantly increased susceptibility enzymatic MMP-2. carboxyl-terminal hemopexin-like domain (PEX) was shown possess critical exodomain properties required interactions cleaved reduced rate an variant deletion PEX. Verifying specificity interactions, isolated PEX competed concentration-dependent manner. These results further elucidated synergistic protease-like fragmentation provide rationale basis modified preparation handling used research.