The myofibroblast, a key cell in normal and pathological tissue repair - PubMed (original) (raw)

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The myofibroblast, a key cell in normal and pathological tissue repair

Ian A Darby et al. Cell Mol Life Sci. 2016 Mar.

Abstract

Myofibroblasts are characterized by their expression of α-smooth muscle actin, their enhanced contractility when compared to normal fibroblasts and their increased synthetic activity of extracellular matrix proteins. Myofibroblasts play an important role in normal tissue repair processes, particularly in the skin where they were first described. During normal tissue repair, they appear transiently and are then lost via apoptosis. However, the chronic presence and continued activity of myofibroblasts characterize many fibrotic pathologies, in the skin and internal organs including the liver, kidney and lung. More recently, it has become clear that myofibroblasts also play a role in many types of cancer as stromal or cancer-associated myofibroblast. The fact that myofibroblasts are now known to be key players in many pathologies makes understanding their functions, origin and the regulation of their differentiation important to enable them to be regulated in normal physiology and targeted in fibrosis, scarring and cancer.

Keywords: Cancer stroma; Contractility; Excessive scarring; Extracellular matrix; Fibrosis; Innervation; α-Smooth muscle actin.

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Figures

Fig. 1

Fig. 1

Human hypertrophic scar tissue stained with α-SM actin antibody. Myofibroblasts persist in nodules in the dermis shown in a. The epidermis is indicated by E. Small vessels stain positively for α-SM actin (short arrows), while myofibroblasts are also positive (long arrow). In b myofibroblasts are seen as long spindle-shaped cells, often aligned in groups (long arrow), while small vessels are also α-SM actin-positive (short arrow). Bar 100 μm

Fig. 2

Fig. 2

Myofibroblasts are found in many pathological situations in response to chronic injury or present in the stroma in and around several types of tumour. Myofibroblasts can also be induced by injury such as bile duct ligation or cholestasis in the liver (a). Stromal staining of myofibroblasts (indicated by arrows) in tumours such as colorectal cancer (b) and liver cancer (cholangiocarcinoma) (c). In c the intimate relationship between tumour cells and myofibroblasts is seen. In many cases, stromal staining of myofibroblasts is a marker of poor prognosis. In addition to their contractile role, myofibroblasts secrete ECM molecules that influence mechanical signalling and cell adhesion. The matricellular protein periostin is secreted by myofibroblasts (positive staining indicated by arrows) and has been shown to be important in tumour growth and in establishment of a metastatic niche (d). Bar 100 μm

Fig. 3

Fig. 3

Myofibroblasts can be derived from various cellular origins, including local fibroblasts, epithelial cells (via EMT), hepatic stellate cells and pericytes. Understanding the regulation of myofibroblast differentiation and survival provides strategies for down-regulating myofibroblast activity and possibly either inducing apoptosis of myofibroblasts or stimulating their dedifferentiation

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