Cells in focus
Fibroblasts and myofibroblasts: Their source, function and role in disease

https://doi.org/10.1016/j.biocel.2006.11.005Get rights and content

Abstract

Fibroblasts are found in most tissues of the body. They exhibit several phenotypes including non-contractile fibroblasts, contractile myofibroblasts, and intermediate phenotypes including the protomyofibroblast. Fibroblasts are metabolically active cells which play critical roles regulating extracellular matrices, interstitial fluid volume and pressure, and wound healing. Fibroblast numbers can be maintained or expanded by proliferation of resident populations but in addition, recent evidence indicates they can also be derived through epithelial-mesenchymal transition or from circulating and tissue-derived mesenchymal stem cells. Many diseases are associated with dysregulation of the injury repair response and fibroblast function, leading to increased or decreased deposition of extracellular matrix proteins, altered tissue architecture, impaired function and in some cases significant morbidity and mortality. There are currently no specific therapies that target fibroblast-associated pathology but increasing knowledge of pathological mechanisms has led to development of new agents providing hope for improved treatment of these diseases.

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.

Section snippets

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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