2‐Methoxyestradiol Inhibits the Oxygen‐Sensing Pathway in Keloid Fibroblasts by Targeting <scp>HIF</scp>‐1α/<scp>PHD</scp>

Maintaining oxygen homeostasis is a basic cellular process for adapting to physiological oxygen variations in which the oxygen-sensing pathway plays a critical role, especially in tumour progression. Little is known about the activity of the oxygen-sensing pathway in keloid tissue. In this study, key features of the oxygen-sensing pathway and its downstream effects were evaluated and compared between normal skin tissue and keloid tissue. Keloid tissue showed increased oxygen-sensing pathway activation and a higher expression of key downstream factors such as tumour necrosis factor-1α (TNF-α) and vascular endothelial growth factor (VEGF). In addition, the effects of 2-methoxyestradiol on the oxygen-sensing pathway in both hypoxic and normoxic keloid fibroblasts were evaluated. Our results suggest that 2-methoxyestradiol could be used to inhibit keloid fibroblast activity by inhibiting the oxygen-sensing pathway and its downstream effectors.