Human tissue factor pathway inhibitor-2 does not bind or inhibit activated matrix metalloproteinase-1.
Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor associated with the extracellular matrices of vascular cells. A recent report provided in vitro evidence that TFPI-2 may be a novel inhibitor of the matrix metalloproteinases MMP-1, MMP-13, MMP-2 and MMP-9. In studies aimed at identifying the structural elements of TFPI-2 mediating the putative inhibition of the above MMPs, we re-examined the ability of native TFPI-2 to form complexes with MMP-2, MMP-9 and MMP-1, as well as assess its ability to inhibit the proteolytic activity of the interstitial collagenase, activated MMP-1. We report here that TFPI-2 failed to form complexes with MMP-2, MMP-9 and MMP-1 as revealed in immunoprecipitation and ligand blotting studies. In addition, TFPI-2 had no influence on the proteolytic activity of activated MMP-1 towards triple-helical collagen. These data provide presumptive evidence that TFPI-2 does not bind to MMP-2, MMP-9 and MMP-1, or regulate MMP-1, in the extracellular matrix.
Du
Xin
X
Department of Pathology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA.
Chand
Hitendra S
HS
Kisiel
Walter
W
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000378:metabolism*
D006023:Glycoproteins; D046911:Macromolecular Substances; D015842:Serine Proteinase Inhibitors; C021240:tissue-factor-pathway inhibitor 2; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1