Roles of the HIF-1α pathway in the development and progression of keloids

Keloids, a pathological scar that is induced by the consequence of aberrant wound healing, is still a major global health concern for its unsatisfactory treatment outcomes. HIF-1α, a main regulator of hypoxia, mainly acts through some proteins or signaling pathways and plays important roles in a variety of biological processes. Accumulating evidence has shown that HIF-1α played a crucial role in the process of keloid formation. In this review, we attempted to summarize the current knowledge on the association between HIF-1α expression and the development and progression of keloids. Through a comprehensive analysis, the molecular mechanisms underlying HIF-1α in keloids were shown to be correlated to the proliferation of fibroblasts, angiogenesis, and collagen deposits. The affected proteins and the signaling pathways were multiple. For instance, HIF-1α was reported to promote keloids formation by enhancing angiogenesis, fibroblast proliferation, and collagen deposition through the activation of periostin PI3K/Akt, TGF‐β/Smad and TLR4/MyD88/NF-κB pathway. However, the specific effects of HIF-1α on keloids keloid illnesses in clinical practice is are entirely unclear, and further studies in clinical trials are still warranted. Therefore, an in-depth understanding of the biological mechanisms of HIF-1α in keloid formation is significant to develop promising therapeutic targets for the treatment of keloids in clinical practice.