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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