Role of Myofibroblast in normal and pathological tissue repair


Tissue repair is an essential phenomenon allowing tissues and organs to recover functional properties that have been lost after an injury, either linked to a wound or to a disease. In fetal or embryonic wounds that repair without a scar or fibrosis, normal repair in the adult always leads to scar formation. In these processes of  myofibroblat  play a crucial role. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by myofibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete.
Normal wound healing
After injury the healing process allow immediately restoration of injured tissue. Wound healing proceeds in three interrelated stages with overlapping time Period. According to morphological changes in the course of the healing process, these stages are described as an inflammatorystage, a proliferative stages for the development of granulation tissue, and a regeneration stages for maturation, scar formation and re-re-epithelialization. The inflammatory stage begins with damage to the capillaries, which triggers the formation of a blood clot consisting of fibrin and fibronectin. These provisional matrixes fill in the lesion and allow different cells to migrate into wound. Platelets present in the blood clot release multiple chemokines which join in the recruitment not only of inflammatory cells (neutrophils and macrophages), but also fibroblasts and endothelial cells. Proliferative stage is the second stage of wound healing. Active angiogenesis which is critical for the wound healing process, allows new capillaries to deliver nutrients including oxygen to the wound, and contributes to the proliferation of fibroblasts. Then fibroblasts become activated and acquire a smooth muscle cell-like phenotype; they are consequently called myofibroblasts. These myofibroblastic cells synthesize and deposit the extracellular matrix components which will replace the provisional matrix.




Pathological repair
Pathological wound healing can be encountered in a variety of disease states. These abnormal repair processes are the result of an impaired remodeling of the granulation tissue for example to abnormal cutaneous repair as s in hypertrophic scarring or to fibrosis in internal organs such as the liver, lung and kidney. In internal organs, after an acute and moderate lesion, the injured tissue may be almost completely restored to normal. The repair process involved is similar to the process in cutaneous wounding.  When the noxious stimulus responsible for the lesion persists, excessive extracellular matrix deposition and the continued presence of myofibroblasts. This excess of extracellular matrix deposition matrix synthesis and degradation by myofibroblasts. For example, in the liver, several chronic diseases are responsible for the development of a significant fibrosis, whose ultimate stage, cirrhosis, has a substantial impact on morbidity and mortality. As in pathological cutaneous wound healing, the installation and persistence of fibrosis is the consequence of an extracellular matrix.


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