title: The extracellular matrix: an active or passive player in fibrosis?
abstract: Fibrosis is characterized by excessive accumulation of collagen and other extracellular matrix (ECM) components, and this process has been likened to aberrant wound healing. The early phases of wound healing involve the formation of a provisional ECM containing fibrin, fibrinogen, and fibronectin. Fibroblasts occupy this matrix and proliferate in response to activators elaborated by leukocytes that have migrated into the wound and are retained by the ECM. This coincides with the appearance of the myofibroblast, a specialized form of fibroblast whose differentiation is primarily driven by cytokines, such as transforming growth factor-β (TGF-β), and by mechanical tension. When these signals are reduced, as when TGF-β secretion is reduced, or as in scar shrinkage, myofibroblasts undergo apoptosis, resulting in a collagen-rich, cell-poor scar. Retention of myofibroblasts in fibrosis has been described as the result of imbalanced cytokine signaling, especially with respect to levels of activated TGF-β. ECM components can regulate myofibroblast persistence directly, since this phenotype is dependent on extracellular hyaluronan, tenascin-C, and the fibronectin splice variant containing the "extra domain A," and also, indirectly, through retention of TGF-β-secreting cells such as eosinophils. Thus the ECM is actively involved in both cellular and extracellular events that lead to fibrosis. Targeting components of the ECM as cells respond to injury and inflammatory stimuli holds promise as a means to avoid development of fibrosis and direct the wound-healing process toward reestablishment of a healthy equilibrium.
authors.affiliation: Hope Heart Matrix Biology Program, Benaroya Research Institute, 1201 Ninth Ave., Seattle, WA 98101, USA. twight@benaroyaresearch.org
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Susan
authors.initials: S
authors.lastname: Potter-Perigo
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*