A Review of the Evidence for and against a Role for Mast Cells in Cutaneous Scarring and Fibrosis

Abstract

Scars are generated in mature skin as a result of the normal repair process, but the replacement of normal tissue with scar tissue can lead to biomechanical and functional deficiencies in the skin as well as psychological and social issues for patients that negatively affect quality of life. Abnormal scars, such as hypertrophic scars and keloids, and cutaneous fibrosis that develops in diseases such as systemic sclerosis and graft-versus-host disease can be even more challenging for patients. There is a large body of literature suggesting that inflammation promotes the deposition of scar tissue by fibroblasts. Mast cells represent one inflammatory cell type in particular that has been implicated in skin scarring and fibrosis. Most published studies in this area support a pro-fibrotic role for mast cells in the skin, as many mast cell-derived mediators stimulate fibroblast activity and studies generally indicate higher numbers of mast cells and/or mast cell activation in scars and fibrotic skin. However, some studies in mast cell-deficient mice have suggested that these cells may not play a critical role in cutaneous scarring/fibrosis. Here, we will review the data for and against mast cells as key regulators of skin fibrosis and discuss scientific gaps in the field.

Hyperbaric oxygen treatment on keloid tumor immune gene expression

“…[ 7 , 25 ] Mast cells were also suggested to be an important type of immune cell in keloid development. [ 26 ] Macrophage is suggested as a type of fibrosis-promoting cell because of the role of its M2 phenotype in fibrosis, but the role of T lymphocyte is more complex. [ 25 ] Little conclusion regarding the roles of T-cell subtypes in scar formation has yet been known.…”

“…[ 25 ] Positive correlation between mast cells and the degree of scar have been demonstrated in literature. [ 26 – 28 ]…”

mMCP7, a Mouse Ortholog of δ Tryptase, Mediates Pelvic Tactile Allodynia in a Model of Chronic Pelvic Pain

“…Mast cells are a multi-functional cell type that play key roles in the pathophysiological processes like host defense, regulation of vascular tone and permeability, angiogenesis, cell recruitment, tissue remodeling, and neural activities (58). Mast cells modulate these biological activates by degranulation and the release of factors including histamines, TNFα, carboxypeptidase A, tryptases, serotonins, dopamine, chymases, VEGF, and NGF (8,10,(59)(60)(61)(62)(63)(64). mMCP7 is able to act directly on mast cells and trigger its activation independent of degranulation (data not shown).…”

Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

“…This will significantly enhance the expression of α-SMA in human lung fibroblasts [ 93 ]. The role of histamine in the stimulation of fibrosis in human skin has also been reported [ 94 ]. Nonetheless, some studies have shown that histamine can inhibit the expression of α-SMA in human skin fibroblasts induced by TGF-β1 through the activation of the H1R receptor [ 95 ].…”

“…Vascular degeneration is the main physiological process in the remodeling stage, which results in the transformation of granulation tissue into collagen-rich scar avascular tissue [ 117 ]. Although there are some objections [ 118 , 119 ], the vast majority of studies support the involvement of MCs in the process of scar formation [ 94 , 120 ]. In addition to mediators, GJIC between MCs and fibroblasts or myofibroblasts in granulation tissue also acts as a bridge of cellular communication, mediating excessive fibrosis [ 81 ].…”