Molecular mechanisms of keloid development

Keloids are benign, fibroproliferative skin lesions that result from abnormal wound healing. This review provides a current understanding of keloid pathogenesis, emphasizing the roles of genetic predisposition, dysregulated molecular pathways, and external influences. While genetic studies revealed familial inheritance patterns and specific polymorphisms, such as rs8032158 in NEDD4 , which contribute to an increased risk of keloid development, a rare congenital syndromes suggest a broader spectrum of genetic susceptibility. At the molecular level, key features of keloid formation include dysregulated fibroblast activity, excessive deposition of extracellular matrix components, and persistent inflammation mediated by various growth factors, cytokines, and chemokines. Crucial signaling pathways, including TGF-β/Smad, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), mitogen-activated protein kinase (MAPK), PI3K/Akt/mTOR, and Wnt/β-catenin are implicated in the activation of fibroblasts and the overproduction of collagen. Furthermore, external factors such as mechanical tension, elevated blood pressure, vitamin D deficiency, and psychological stress may exacerbate keloid formation, although the precise mechanisms involved remain partially understood. By synthesizing existing evidence, this review underscores the multifactorial nature of keloid formation and identifies potential therapeutic targets, paving the way for more effective treatment strategies.