title: Coagulation and coagulation signalling in fibrosis.
abstract: Following tissue injury, a complex and coordinated wound healing response comprising coagulation, inflammation, fibroproliferation and tissue remodelling has evolved to nullify the impact of the original insult and reinstate the normal physiological function of the affected organ. Tissue fibrosis is thought to result from a dysregulated wound healing response as a result of continual local injury or impaired control mechanisms. Although the initial insult is highly variable for different organs, in most cases, uncontrolled or sustained activation of mesenchymal cells into highly synthetic myofibroblasts leads to the excessive deposition of extracellular matrix proteins and eventually loss of tissue function. Coagulation was originally thought to be an acute and transient response to tissue injury, responsible primarily for promoting haemostasis by initiating the formation of fibrin plugs to enmesh activated platelets within the walls of damaged blood vessels. However, the last 20years has seen a major re-evaluation of the role of the coagulation cascade following tissue injury and there is now mounting evidence that coagulation plays a critical role in orchestrating subsequent inflammatory and fibroproliferative responses during normal wound healing, as well as in a range of pathological contexts across all major organ systems. This review summarises our current understanding of the role of coagulation and coagulation initiated signalling in the response to tissue injury, as well as the contribution of uncontrolled coagulation to fibrosis of the lung, liver, kidney and heart. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.
authors.affiliation: Centre for Inflammation and Tissue Repair, University College London, Rayne Institute, 5 University St., London WC1E 6JF, UK. Electronic address: paul.mercer@ucl.ac.uk.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Mercer
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Chambers
mesh_terms: D001777:Blood Coagulation; D005337:Fibrin / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007249:Inflammation; D014945:Wound Healing
chemical_list: D005337:Fibrin