The hypothesis of fibroproliferative skin disease is based on the results of the keloid study. Silicone gel wipes for the prevention and treatment of developing hypertrophic and keloid scars. Treatment of hypertrophic and keloid scars with argon and carbon dioxide lasers. Laser treatment of erythematous-hypertrophic and pigmented scars in 26 patients.
Comparison of intramarginal and extra marginal excision of hypertrophic burn scars. An increase in mRNA and proteins of type I and III collagen and TGF-b1 in a hypertrophic burn scar. Increased expression of mRNA that transforms growth factor-b, procollagen type I, and type III in hypertrophic human scar tissue after burns.
Modulation of collagen synthesis by the transformation of growth factor-b into keloid and hypertrophic scar fibroblasts. Differential expression of transforming growth factor I and II beta receptors and activation of Smad 3 in keloid fibroblasts. Benveniste K. The use of antihistamines to slow the growth of fibroblasts derived from human skin, scars, and keloids.
Keloids are fibroproliferative scars that can form after burns or other skin lesions. Keloids are traditionally regarded as scarring in a spectrum of fibroproliferative skin diseases. Keloids are considered to be benign fibroproliferative tumors of the skin that result from abnormal wound healing processes resulting from skin injury. Although keloids share some characteristics with hypertrophic scars, such as excessive collagen deposition, they differ in that keloids can extend beyond the wound margins and rarely regress over time.
In contrast, keloids are aggressive exophytic skin growths that have grown disproportionately beyond the original wound from a source that remains suspended in the process of “wound healing” and scar maturation. In keloids, local hypoxia at the wound site accelerates wound healing by stimulating angiogenesis and inducing fibroblast proliferation (175), as evidenced by the expression of hypoxia-induced vascular endothelial growth factor (VEGF) (176) in keloid fibroblasts and higher blood vessel density in keloids than in normal dermis and scars. In terms of fibroblast proliferation, while fibroblasts are the main cellular ingredients in normal cutaneous scars, they occur in higher density in HS and keloids.
Furthermore, IL-6 has been reported to be highly expressed in HTS tissue fibroblasts compared to normal fibroblasts, influencing scar formation by modulating fibroblasts . Fetal fibroblasts produced less IL-6 than adult fibroblasts, and the addition of exogenous IL-6 caused scarring rather than scarless wound healing . In the HTS rabbit ear model, bFGF was applied daily for three months and there was a decrease in collagen expression and an increase in MMP-1 expression in the wounds so that bFGF appeared to have a negative effect on scarring .
Increased amounts of TGF-b are found in HS, and scarless healing in human fetuses is thought to be a consequence of TGF-b deficiency. Recent studies have also shown that TGF-b is not only involved in the normal wound healing process but also contributes to fibroproliferative diseases such as pulmonary fibrosis and HTS. Abnormal wound healing, mainly caused by chronic inflammation or infection, can lead to fibroproliferative disorders such as hyperhidrosis and keloids. Chemokines are important regulators of various stages of wound healing in humans. Furthermore, inadequate regulation of chemokine networks leads to chronic inflammation, dysregulated vascular development, and the creation of chronic environments that lead to impaired healing, such as HTS. , keloids, scleroderma, psoriasis, and various types of fibrosis and chronic wounds. HTS is hypercellular due to increased fibroblasts and recruitment of non-hematopoietic peripheral cells.
On the one hand, other signaling pathways can induce cellular changes, such as collagen synthesis and secretion, leading to increased scarring. A recent study analyzed samples of keloid and hypertrophic scars and suggested that crosstalk between the TGF-b/Smad and Wnt/b-catenin pathways plays a role in the formation of pathological scars. The development of pathological skin scars, especially hypertrophic (HS) and keloid scars, involves complex pathways, and the exact mechanisms by which pathological skin scars are initiated, developed, and regulated need to be fully elucidated.
The pathogenesis of HS and keloids involves cellular and extracellular components in the epidermis and dermis that are regulated by multiple interfering factors during the phases of inflammation, proliferation, and remodeling. However, to clarify the pathogenesis of keloids, it is necessary to distinguish scar from disease. Hypertrophic scar (HS) is a benign fibroproliferative skin disorder caused by an abnormal wound healing process that can lead to aesthetic and functional impairment in patients. Hypertrophic scar (HTS) is a fibroproliferative disorder of the skin that develops following deep burns, skin injuries, and surgical wounds.
Reconstruction of the scar after a burn of the upper limb with artificial leather. Treatment of keloid scars after sternotomy with a pulsed dye laser with a 585 nm flash lamp. A controlled study of intralesional administration of recombinant interferon-g in the treatment of keloid scars. Combined use of dry destruction and intralesional injections of suspensions of fluorinated adrenocorticoids to reduce keloid and hypertrophic scars.
GDF-9 expression was assessed in tissue samples from surgically removed keloids and hypertrophic scars and compared with that in normal skin tissues using qRT-PCR. Western blotting confirmed the results, which show greater expression of the GDF-9 protein in keloids compared to normal and hypertrophic scar tissue extracts.
In contrast, the expression of anti-fibrotic genes such as TGF-b3 and DCN was significantly up-regulated. 20 BM-MSCs improve wound healing and prevent HTS formation through regulation of inflammation, differentiation, and release of angiogenic and/or paracrine factors.
These studies implicate BM-MSCs in the pathogenesis of hypertrophic scarring and suggest their therapeutic potential for HTS. Compared with normal scars, HS had more epidermal LC, higher expression of epidermal interleukin 4, and decreased expression of epidermal interleukin, suggesting impaired epidermal regulation of dermal remodeling in HS formation. 11 12 In contrast, in keloids, the number of intraepidermal LCs was not significantly different from that in normal scars or normal skin, but cells such as T cells, B cells, and replacement macrophages (M2) were more infiltrated. The study’s data suggest that galanin can alleviate skin scarring through the TGF-b/Smad signaling pathway, possibly by upregulating the expression of Smad 7, thereby inhibiting the expression of collagen types I and III and TGF.-b1.