title: Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ' as thrombomobulin II.
abstract: Fibrin is an important matrix protein that provides the backbone to the blood clot, promoting tissue repair and wound healing. Its precursor fibrinogen is one of the most heterogeneous proteins, with an estimated 1 million different forms due to alterations in glycosylation, oxidation, single nucleotide polymorphisms, splice variation and other variations. Furthermore, ligation by transglutaminase factor XIII (cross-linking) adds to the complexity of the fibrin network. The structure and function of the fibrin network is in part determined by this natural variation in the fibrinogen molecule, with major effects from splice variation and cross-linking. This mini-review will discuss the direct effects of fibrinogen αEC and fibrinogen γ' splice variation on clot structure and function and also discuss the additional role of fibrinogen γ' as thrombomodulin II. Furthermore, the effects of cross-linking on clot function will be described. Splice variation and cross-linking are major determinants of the structure and function of fibrin and may therefore impact on diseases affecting bleeding, thrombosis and tissue repair.
authors: Thrombosis and Tissue Repair Group, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK.
authors: Cédric
authors: C
authors: Duval
authors: Thrombosis and Tissue Repair Group, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK. Electronic address: r.a.s.ariens@leeds.ac.uk.
authors: Robert A S
authors: RAS
authors: Ariëns
mesh_terms: D017398:Alternative Splicing; D001777:Blood Coagulation / Q000502:physiology; D003432:Cross-Linking Reagents; D005176:Factor XIII / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005337:Fibrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015241:Fibrinogens, Abnormal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D018180:Thrombomodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: D003432:Cross-Linking Reagents; D015241:Fibrinogens, Abnormal; D020033:Protein Isoforms; C546931:THBD protein, human; D018180:Thrombomodulin; C527521:fibrinogen gamma'; D005337:Fibrin; D005176:Factor XIII
keywords: Cross-linking; Fibrin clot; Fibrinogen; Splice-variant