Secreted Factors from Keloid Keratinocytes Modulate Collagen Deposition by Fibroblasts from Normal and Fibrotic Tissue: A Pilot Study

Abstract

<jats:p>Interactions between keratinocytes and fibroblasts in the skin layers are crucial in normal tissue development, wound healing, and scarring. This study has investigated the role of keloid keratinocytes in regulating collagen production by primary fibroblasts in vitro. Keloid cells were obtained from removed patients’ tissue whereas normal skin cells were discarded tissue obtained from elective surgery procedures. Fibroblasts and keratinocytes were isolated, cultured, and a transwell co-culture system were used to investigate the effect of keratinocytes on collagen production using a ‘scar-in-a-jar’ model. Keloid fibroblasts produced significantly more collagen than normal skin fibroblasts in monoculture at the RNA, secreted protein, and stable fibrillar protein level. When keloid keratinocytes were added to normal skin fibroblasts, expression of collagen was significantly upregulated in most samples, but when added to keloid fibroblasts, collagen I production was significantly reduced. Interestingly, keloid keratinocytes appear to decrease collagen production by keloid fibroblasts. This suggests that signaling in both keratinocytes and fibroblasts is disrupted in keloid pathology.</jats:p>

Defining a Unique Gene Expression Profile in Mature and Developing Keloids

“…Efforts to target and suppress fibroblasts in keloids have led to strategies such as regulating fibroblasts for scarless wound healing ( Zou et al., 2021 ) or inhibiting keloid-derived fibroblast growth and migration with LY2109761 ( Wang et al., 2021 ). In tandem, keratinocytes secrete factors that modulate fibroblast collagen production ( Alghamdi et al., 2020 ), and mast cells play an important role in dermal scarring ( Ud-Din et al., 2020 ) by interacting with fibroblasts in epithelial growth and regeneration ( Artuc et al., 2002 ). Bulk deconvolution showed unsurprising increases in fibroblasts, endothelial cells, and M2 macrophages/dendritic cells in keloid skin.…”

Cellular Mechanisms and Therapies in Wound Healing: Looking toward the Future

“…Interestingly, keloid keratinocytes appear to decrease collagen production by keloid fibroblasts. The authors suggested that signaling in both keratinocytes and fibroblasts is disrupted in keloid pathology (for more details about this article, see [ 9 ]).…”

Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity

“…Keloids are fibrotic skin diseases that occur at areas with a cutaneous injury. They typically extend beyond boundaries of the original wound (1)(2)(3)(4)(5)(6)(7)(8). They are characterized by excessive collagen deposition and abnormal cellular proliferation (5)(6)(7)(8)(9).…”

“…They typically extend beyond boundaries of the original wound (1)(2)(3)(4)(5)(6)(7)(8). They are characterized by excessive collagen deposition and abnormal cellular proliferation (5)(6)(7)(8)(9). Keloids can be pruritic near the site of injuries.…”