Role of HIF‐1α in pathogenic mechanisms of keloids

Abstract

Backgrouds and Objective Keloids are defined as overrepairing products that develop after skin lesions. Keloids are characterized by the proliferation of fibroblasts and the overaccumulation of extracellular matrix components (mainly collagen), leading to a locally hypoxic microenvironment. Hence, this article was aimed to review hypoxia in pathogenesis of keloids. Methods We reviewed and summarized the relevant published studies. Results Hypoxia results in the accumulation of hypoxia‐inducible factor 1α (HIF‐1α) in keloids, contributing to overactivation of the fibrotic signaling pathway, epithelial–mesenchymal transition, and changes in metabolism, eventually leading to aggravated fibrosis, infiltrative growth, and radiotherapy resistance. Conclusion It is, therefore, essential to understand the role of HIF‐1α in the pathogenic mechanisms of keloids in order to develop new therapeutic approaches.

Identification of Collagen-Suppressive Agents in Keloidal Fibroblasts Using a High-Content, Phenotype-Based Drug Screen

“…Previous reports ( Kang et al, 2020 ; Lei et al, 2019 ; Qiu et al, 2023 ; Zhang et al, 2006 ) have suggested that keloid tumors likely exist in a state of relative hypoxia, which is at odds with standard cell culture incubators (ie, 20% oxygen). A high-content screen ( Figure 1 ) that can profile drug effects in tissue conditions (ie, hypoxia) was developed.…”

“…Furthermore, standard assay conditions such as 20% oxygen may not be consonant with in vivo drug effects because the dermal tissue oxygen concentration is reported to be 1–4% ( Wang et al, 2003 ). Several groups have documented the expression of HIF1-a in human keloidal tissue, suggesting that the in situ ambient oxygen might be even less ( Kang et al, 2020 ; Lei et al, 2019 ; Qiu et al, 2023 ; Zhang et al, 2006 ). Taken together, there is a clear need to devise a screen in tissue conditions using secreted collagen as the phenotypic endpoint and 1% oxygen to hypoxia.…”

Insights into How Plant-Derived Extracts and Compounds Can Help in the Prevention and Treatment of Keloid Disease: Established and Emerging Therapeutic Targets

“…Hypoxia has been shown to promote proliferation and inhibit the apoptosis of KFs via the HIF-1α-dependent mechanism, and these responses could be modulated pharmacologically using resveratrol [63]. Thus, research on the role of HIF-1α in keloid pathogenesis would provide a new opportunity to develop therapeutic approaches [64].…”

Peculiarities of Changes in the Balance of the Angiogenesis Regulators and Activities of Matrix Metaloproteinases -2, -9 in Chronic Ulcers in Diabetic Patients

“…Крім того, надекспресія HIF-1 корелює з посиленою експресією профіброзних факторів і надмірною фіброгенною відповіддю, що призводить до розвитку келоїдних і гіпертрофічних рубців [12].…”