Perspective Article: Tissue repair, contraction, and the myofibroblast

Abstract

After the first description of the myofibroblast in granulation tissue of an open wound by means of electron microscopy, as an intermediate cell between the fibroblast and the smooth muscle cell, the myofibroblast has been identified both in normal tissues, particularly in locations where there is a necessity of mechanical force development, and in pathological tissues, in relation with hypertrophic scarring, fibromatoses and fibrocontractive diseases as well as in the stroma reaction to epithelial tumors. It is now accepted that fibroblast/myofibroblast transition begins with the appearance of the protomyofibroblast, whose stress fibers contain only beta- and gamma-cytoplasmic actins and evolves, but not necessarily always, into the appearance of the differentiated myofibroblast, the most common variant of this cell, with stress fibers containing alpha-smooth muscle actin. Myofibroblast differentiation is a complex process, regulated by at least a cytokine (the transforming growth factor-beta1), an extracellular matrix component (the ED-A splice variant of cellular fibronectin), as well as the presence of mechanical tension. The myofibroblast is a key cell for the connective tissue remodeling that takes place during wound healing and fibrosis development. On this basis, the myofibroblast may represent a new important target for improving the evolution of such diseases as hypertrophic scars, and liver, kidney or pulmonary fibrosis.

Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

“…The MSC-treated animals showed less fibrosis, but they had a reduced glomerulosclerosis index. These partially improved outcomes were also seen following other therapeutic strategies, such as MMF therapy, using the remnant model, where glomerular and interstitial injuries were attenuated despite persistent proteinuria [13,41]. Interestingly, anemia was also reduced in MSC-treated animals.…”

Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis

“…On the other hand, the persistence, proliferation and migration of the myofibroblast in chronically injured tissues leads to fibrosis and provides a favourable environment for tumour cell growth and invasion. [1][2][3][4][5][6] Controlled transdifferentiation offers the prospect of the optimisation of wound healing by regulating the conversion of resident differentiated cells into myofibroblasts. In the present study, we provide evidence that global reprogramming of gene expression during the conversion of an HSC to a myofibroblast is subject to epigenetic control.…”

“…Severe or chronic injury is associated with persistence and proliferation of wound healing myofibroblasts and formation of crosslinked scars also known as fibrotic tissue. 1 Fibrosis is a disease process common to major organs such as the kidney, liver, pancreas, heart and lungs in the context of reiterative injury or infection. [2][3][4][5] Recent evidence also suggests that the stroma reaction, in which tumours benefit from the antiapoptotic and growth promoting properties of their surrounding ECM, is driven by myofibroblast secretion of collagen-rich ECM into the extracellular space surrounding the growing tumour.…”

FAK Is Required for TGFβ-induced JNK Phosphorylation in Fibroblasts: Implications for Acquisition of a Matrix-remodeling Phenotype

“…The type of fibroblast that executes this function is the myofibroblast, socalled because this cell type expresses ␣-smooth muscle actin (␣-SMA), which is organized into stress fibers that exert contractile forces on the ECM through specialized cell surface structures called focal adhesions (Hinz and Gabbiani, 2003). In a properly healed wound, few myofibroblasts remain; however, if myofibroblasts persist in the lesion, scarring results (Desmouliere et al, 2005). Excessive scarring can lead to chronic fibrosis, which can result in organ failure and death.…”