Cells in focusFibroblasts and myofibroblasts: Their source, function and role in disease
Introduction
Fibroblasts are spindle shaped cells found in the majority of tissues and organs of the body associated with extracellular matrix (ECM) molecules. Characteristic features include expression of vimentin in the absence of desmin and α-smooth muscle actin. When activated, fibroblasts exhibit an abundant endoplasmic reticulum and prominent Golgi associated with the synthesis and secretion of ECM molecules including collagens, proteoglycans and fibronectin, as well as, proteases capable of degrading the ECM. Cytoskeletal proteins in association with cell surface integrins and the ECM facilitate cell motility and the generation of contractile forces important in tissue homeostasis and wound healing.
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Cell origin and plasticity
Fibroblasts are embryologically of mesenchymal origin with a spectrum of phenotypic entities ranging from the non-contractile fibroblast to the contractile myofibroblast with a number of intermediate phenotypes having been described (reviewed in Eyden, 2005) including that of the protomyofibroblast (Desmouliere, Darby, & Gabbiani, 2003). In addition to the features of active fibroblasts, prototypical myofibroblasts are distinguished by the presence of α-smooth muscle actin containing stress
Functions
One of the major functions of fibroblasts is the production and homeostatic maintenance of the ECM of the tissue or organ in which they reside. They are metabolically highly active cells, being capable of synthesising and secreting most ECM components, including collagens, proteoglycans, fibronectin, tenascin, laminin and fibronectin. Fibroblasts continually synthesise ECM proteins and it has been estimated that each cell can synthesise approximately 3.5 million procollagen molecules/cell/day (
Associated pathologies
Many diseases associated with diminished or excess deposition of ECM are likely to be related to dysregulation of the injury repair response and fibroblast function. In this context ‘injury’ is broad ranging including environmental, infectious, cancerous, traumatic/mechanical, autoimmune and drug-induced insults. Thus, diseases in which fibroblasts, in their various phenotypic guises, play a central role may affect almost all tissues and organs of the body (illustrated in Fig. 1). Their
Acknowledgements
RJMs research is supported by grants from the Wellcome Trust, British Lung Foundation and Asthma UK.
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