Myofibroblasts: Functions, evolution, origins, and the role in disease

Abstract

Fibroblasts are ubiquitous mesenchymal cells, normally present in the stroma of many tissues of the body. They exhibit spindle shape morphology. There is phenotypic heterogeneity among fibroblasts. Fibroblasts are generally stress shielded by cross-linked extracellular matrix (ECM). This protective structure is lost as it differentiates to myofibroblasts (MFs). MFs are characterized by bundles of actin microfilaments (stress fibers) containing α-smooth muscle actin (α-SMA). Diverse cell types contribute to the appearance of MF subpopulation. A soluble factor transforming growth factor-β1 is considered a major growth factor that directly promotes MF development by inducing α-SMA expression. Modulation of fibroblast to MF represents a key event in wound healing process. They are also known to be involved in diverse reactive proliferative conditions, pathological remodeling, fibrosis, oral submucous fibrosis and in stroma of invasive and metastatic carcinoma odontogenic cysts/tumors and odontogenic cysts/tumors. This review describes its functions, evolution, multiple origins, and highlights on its role in the pathological state in relation to the oral cavity.

Keywords

• extracellular matrix
• fibroblasts
• fibrosis
• mesenchymal cells
• myofibroblasts
• stroma reaction
• transforming growth factor-β
• wound healing