Background: Pressure ulcers are refractory skin ulcers that frequently develop at pressure sites in elderly individuals and those with reduced physical activity, and effective preventive strategies are urgently needed.These ulcers are primarily caused by cutaneous ischemiareperfusion (I/R) injury, in which inflammation and oxidative stress play important roles.JAK inhibitors are widely used for inflammatory disorders and are also known to possess antioxidant effects.However, their therapeutic potential in cutaneous I/R injury remains unclear.Objective: This study aimed to investigate the role of JAK/STAT signaling and the efficacy of the selective JAK2/3 inhibitor AG490 in preventing ulcer formation in a murine cutaneous I/R model. Methods:In vivo, mice underwent four cycles of 3h ischemia followed by 1h reperfusion using magnetic skin compression.AG490 or vehicle was administered intraperitoneally before ischemia.In vitro, 10T1/2 cells were subjected to an oxygen-glucose deprivation/reoxygenation (OGD/R) model. Results:Cutaneous I/R induced phosphorylation of JAK2 and STAT3, which was suppressed by AG490.On day 3, ulcer areas were significantly smaller in AG490-treated mice.AG490 also reduced inflammatory cell infiltration, apoptosis, and hypoxia, while enhancing Nrf2 activity in Keap1-dependent oxidative stress detector-luciferase (OKD-LUC) mice.In vitro, AG490 suppressed OGD/R-induced JAK/STAT activation, attenuated ROS production, prevented cell death, and enhanced the expression of HO-1. Conclusion:We demonstrated the protective effect of AG490 against I/R-induced skin damage through the attenuation of inflammation and oxidative stress, highlighting JAK inhibition as a promising approach for pressure ulcer prevention.
Saito et al. (Sun,) studied this question.