Wound healing in autophagy-deficient mice

Approximately 9-12 million Americans suffer from chronic wounds, which have profound physical, emotional, and financial impacts on affected individuals. Due to an aging population and rising rates of diabetes, chronic wounds represent a dire and expanding public health crisis. We hypothesized that autophagy is a process in which cellular material is captured in autophagosomes that fuse with lysosomes, where the contents are degraded and recycled, is required for timely wound healing. We discovered that autophagosomes are more abundant in wounded human and mouse tissue than control, normal skin. Using genetically engineered mouse models with knockout of autophagy protein ATG7 (Atg7-KO mice), we found that wounds introduced into Atg7-KO mice heal more slowly than autophagy-proficient littermates. Wounded Atg7-deficient mice exhibit a prolonged inflammatory phase associated with acute inflammation and pro-inflammatory cytokines, characteristics frequently observed in human patients with chronic wounds. Tissue-specific autophagy inactivation supports a role for autophagy induction in macrophages for timely healing. Wounds and macrophages from autophagy-deficient mice contained higher levels of NF-kB activity than controls, and treatment with a small molecule NF-kB pathway inhibitor partially reversed the slower healing in autophagy-deficient mice. Analysis of human wounds revealed higher levels of autophagosomes in acute, healing, surgical wounds than a chronic wound from the same individual. Our findings support a role for autophagy in promoting the transition from the inflammatory to the reparative phases of wound healing. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.