关键词: YAP/TAZ dermal fibroblasts fibrosis skin regeneration verteporfin

Mesh : Verteporfin / pharmacology therapeutic use Humans Collagen / metabolism Fibroblasts / drug effects metabolism Animals Wound Healing / drug effects Antifibrotic Agents / pharmacology therapeutic use Cells, Cultured Tissue Scaffolds / chemistry Cicatrix / drug therapy pathology metabolism Male Fibrosis Skin / drug effects pathology metabolism

来  源:   DOI:10.1134/S0006297924050146

Abstract:
Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel application as a wound dressing and fibroblast attractant with verteporfin as an antifibrotic agent was examined in vivo and in vitro. In vitro effects of verteporfin on viability and myofibroblast markers expression were evaluated using fibroblasts isolated from human scar tissue. In vivo the collagen gel and verteporfin (individually and in combination) were applied into the wound to investigate scarring during skin regeneration: deviations in skin layer thickness, collagen synthesis, and extracellular matrix fibers were characterized. The results indicate that verteporfin reduces fibrotic phenotype by suppressing expression of the contractile protein Sm22α without inducing cell death. However, administration of verteporfin in combination with the collagen gel disrupts its ability to direct wound healing in a scarless manner, which may be related to incompatibility of the mechanisms by which collagen and verteporfin control regeneration.
摘要:
广泛的皮肤损伤需要刺激再生过程而不形成疤痕的专门治疗。在体内和体外检查了将胶原蛋白凝胶应用作为伤口敷料和成纤维细胞引诱剂与维替泊芬作为抗纤维化剂结合使用的可能性。使用从人瘢痕组织分离的成纤维细胞评估维替泊芬对活力和肌成纤维细胞标志物表达的体外作用。在体内,将胶原蛋白凝胶和维替泊芬(单独和组合)应用于伤口,以研究皮肤再生过程中的瘢痕形成:皮肤层厚度的偏差,胶原蛋白合成,和细胞外基质纤维进行了表征。结果表明,维替泊芬通过抑制收缩蛋白Sm22α的表达而不诱导细胞死亡来减少纤维化表型。然而,维替泊芬与胶原蛋白凝胶的联合给药破坏了它以无疤痕的方式指导伤口愈合的能力,这可能与胶原蛋白和维替泊芬控制再生的机制不相容性有关。
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