title: Matrix metalloproteinase12 facilitated platelet activation by shedding carcinoembryonic antigen related cell adhesion molecule1.
abstract: Platelets express several MMPs that modulate their activation, which in turn regulates thrombosis, but the exact mechanism is unclear. This study evaluated the platelet expression of MMP12 and platelet activation by shedding CEACAM1 mediated by MMP12. Expression of MMP12 was measured by RT-PCR, Western blot (WB), and casein zymography in platelet from whole blood by gel filtration over plateletpheresis. The site of CEACAM1 cleavage by MMP12 was determined by high performance liquid chromatography (HPLC), mass spectrometry, WB and flow cytometry (FCM). Furthermore, the regulation of platelet aggregation, release and adhesion by MMP12-dependent shedding of platelet CEACAM1 was analyzed. We have observed that human platelets express MMP12. In addition, CEACAM1 as enzymatic substrates of MMP12 have also been found in this study. MMP12 can cleave the CEACAM1 exodomain at several sites and generated several short peptides. Among these fragments, one peptide, WYKG was identified, whose cutting sits were S66/W67 and A83/I84. We also found that MMP12 facilitated type I collagen induced platelet aggregation, adhesion and alpha granule secretion. Similarly, one short peptide, WYKG, facilitated type I collagen induced platelet alpha granule secretion. We conclude that platelet express MMP12 may facilitate platelet activation through shedding of CEACAM1.
authors.affiliation: Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Wei
authors.affiliation: Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China.
authors.forename: Si
authors.initials: S
authors.lastname: Lu
authors.affiliation: Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, PR China. Electronic address: zhhmeng@aliyun.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Meng
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D015539:Platelet Activation / Q000276:immunology*; D010973:Platelet Adhesiveness / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Carcinoembryonic antigen related cell adhesion molecule1; Matrix metalloproteinase12; Platelet