Myofibroblast biology and interactions with the environment

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Normal tissue repair includes a number of overlapping phases. After injury, there is usually an early inflammatory step. Next, as granulation tissue forms, fibroblasts invade the wound and begin to replace the provisional matrix with a more mature wound matrix. As the granulation tissue phase proceeds, fibroblasts acquire a new phenotype with prominent microfilament bundles. These typical myofibroblasts (MFs) have been shown to develop a smooth muscle-like phenotype, and are responsible for wound contraction. Lastly, in the resolution phase of healing, there is considerable loss of cell types including MFs, by apoptosis. Inappropriate delay of apoptosis, and thus increased survival of MFs activated during the healing process, may be a factor which leads to pathological situations and excessive scarring. In most situations, MFs derive from local connective tissue cells but it has now become clear that other cells can contribute to MF production. Both MF differentiation and apoptosis are dependent on cytokines, mechanical stress and more generally on cell-cell and/or cell-matrix interactions. The control of the MF activity represents an important target to promote healing and to limit excessive scarring.

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