Abstract:

The crucial role played by the myofibroblast in wound healing and pathological organ remodeling is well established; the general mechanisms of extracellular matrix synthesis and of tension production by this cell have been amply clarified. This review discusses the pattern of myofibroblast accumulation and fibrosis evolution during lung and liver fibrosis as well as during atheromatous plaque formation. Special attention is paid to the specific features characterizing each of these processes, including the spectrum of different myofibroblast precursors and the distinct pathways involved in the formation of differentiated myofibroblasts in each lesion. Thus, whereas in lung fibrosis it seems that most myofibroblasts derive from resident fibroblasts, hepatic stellate cells are the main contributor for liver fibrosis and media smooth muscle cells are the main contributor for the atheromatous plaque. A better knowledge of the molecular mechanisms conducive to the appearance of differentiated myofibroblasts in each pathological situation will be useful for the understanding of fibrosis development in different organs and for the planning of strategies aiming at their prevention and therapy.

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The Myofibroblast

Marie Bochaton-Piallat

Giulio Gabbiani

From the Laboratory of Cell Biophysics,^{École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; the Department of Pathology,}^{University of Michigan Medical School, Ann Arbor, Michigan; the Division of Pulmonary and Critical Care Medicine,}^{Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan; the Department of Clinical Pathophysiology,}^{University of Florence, Florence, Italy; and the Department of Immunology and Pathology,}^{C.M.U., University of Geneva, Geneva, Switzerland}

Accepted 2007 Mar 22.

Abstract

The crucial role played by the myofibroblast in wound healing and pathological organ remodeling is well established; the general mechanisms of extracellular matrix synthesis and of tension production by this cell have been amply clarified. This review discusses the pattern of myofibroblast accumulation and fibrosis evolution during lung and liver fibrosis as well as during atheromatous plaque formation. Special attention is paid to the specific features characterizing each of these processes, including the spectrum of different myofibroblast precursors and the distinct pathways involved in the formation of differentiated myofibroblasts in each lesion. Thus, whereas in lung fibrosis it seems that most myofibroblasts derive from resident fibroblasts, hepatic stellate cells are the main contributor for liver fibrosis and media smooth muscle cells are the main contributor for the atheromatous plaque. A better knowledge of the molecular mechanisms conducing to the appearance of differentiated myofibroblasts in each pathological situation will be useful for the understanding of fibrosis development in different organs and for the planning of strategies aiming at their prevention and therapy.

Abstract

After tissue injury, fibroblasts differentiate into contractile and secretory myofibroblasts that contribute to tissue repair during wound healing, but that can severely impair organ function when contraction and extracellular matrix (ECM) protein secretion become excessive, such as in hypertrophic scars, scleroderma, and Dupuytren’s disease as well as in heart and kidney fibrosis.¹23 Moreover, myofibroblasts present in the so-called stroma reaction of epithelial tumors may promote the progression of cancer invasion.⁴ Here, we discuss the role of myofibroblasts in causing pathological deformation of two vital organs, liver³ and lung,⁵ and in contributing to the formation of the atheromatous plaque and restenotic lesions.⁶7 Myofibroblast differentiation is a complex phenomenon that follows distinct patterns in different organs. To counteract therapeutically organ dysfunction caused by myofibroblasts, it is crucial to understand the general molecular pathways regulating their evolution and function to distinguish the mechanisms common to all situations from those specific to a given organ and/or disease.

Footnotes

Address reprint requests to Boris Hinz, Ph.D., Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Bâtiment SG–AA-B143, Station 15, CH-1015 Lausanne, Switzerland. E-mail: hc.lfpe@znih.sirob.

Supported by MUIR grant SM2378 and FiorGen Foundation (to A.G.), the Swiss National Science Foundation grants 3100A0-102150/1 and 3100A0-113733/1 (to B.H.), the Swiss National Science Foundation grant 32-068034.02 (to M.-L.B.P.), the National Institutes of Health grants HL28737, HL31963, HL52285, and HL77297S and an award from the Sandler Program in Asthma Research (to H.P.), and the National Institutes of Health grants HL74024 and HL67967 (to V.J.T.).

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