Gαi1 activation induced by short-term hypoxia promotes epidermal cell migration in wound healing through the Akt-mTOR pathway

Hypoxia is commonly observed in the wound microenvironment; however, the specific mechanism by which it affects epidermal cell migration remains unclear. This study aimed to examine the impact of hypoxia on epidermal cell migration and explore the underlying mechanisms involved. The impact of hypoxia (1 ​% oxygen) on the migration of an immortal keratinocyte cell line, HaCaT, was evaluated using a scratch assay and live cell imaging system. The activation of Gαi1 in HaCaT cells following hypoxia treatment was detected by immunoprecipitation. Possible biological mechanisms were explored through gene microarray assays and bioinformatics methods. Furthermore, the effect of Gαi1 loss-of-function on wound healing was investigated using a rat wound model. Short-term hypoxia significantly enhances HaCaT cell migration and Gαi activation, also observed in rat wound tissue. However, the migration difference between hypoxic and normoxic conditions is negligible after Gαi1 knockdown, highlighting Gαi1's role. Bioinformatics analysis points to the PI3K-Akt pathway as a key mediator, which is confirmed by Akt inhibitor experiments. Additionally, Gαi1 promotes cell migration via the PI3K/Akt/mTORC pathway under hypoxia, and Gαi1 knockdown in rats results in slower wound healing and reduced re-epithelialization. Short-term hypoxia promotes epidermal cell migration through the activation of the Akt-mTOR pathway by Gαi1. Defects in Gαi1 lead to impaired re-epithelialization and delayed wound healing in rats.