AMP‐activated protein kinase inhibition in fibro‐adipogenic progenitors impairs muscle regeneration and increases fibrosis

Abstract Background Following muscle injury, fibro‐adipogenic progenitors (FAPs) are rapidly activated and undergo apoptosis at the resolution stage, which is required for proper muscle regeneration. When excessive FAPs remain, it contributes to fibrotic and fatty infiltration, impairing muscle recovery. Mechanisms controlling FAP apoptosis remain poorly defined. We hypothesized that AMP‐activated protein kinase (AMPK) in FAPs mediates their apoptosis during the muscle regeneration. Methods To test, AMPKα1fl/fl PDGFRαCre mice were used to knock out AMPKα1 in FAPs. Following AMPKα1 knockout, the mice were injected with phosphate‐buffered saline or glycerol to induce muscle injury. Tibialis anterior muscle and FAPs were collected at 3, 7 and 14 days post‐injury (dpi) for further analysis. Results We found that AMPKα1 deletion in FAPs enhanced p65 translocation to the nuclei by 110% (n = 3; P