Background: Delayed healing of diabetic wounds is driven by insufficient angiogenesis and maladaptive immunity. An unbiased screen of wound transcriptomes identified prolactin-induced protein (GCDFP-15) as consistently upregulated. Methods: Utilizing murine diabetic wound models, we investigated the functional role of GCDFP-15 through genetic deletion and topical recombinant protein administration. Results: Genetic deletion of GCDFP-15 accelerated wound closure, enhanced angiogenesis, and promoted a pro-reparative macrophage phenotype. This was mediated by activation of the PI3K/AKT/mTOR/STAT3 signalling axis. Conversely, topical GCDFP-15 impaired repair and inhibited this pathway in knockout mice. Conclusion: GCDFP-15 acts as an endogenous inhibitor of diabetic wound healing by suppressing pro-reparative signalling. Targeting GCDFP-15 may represent a novel therapeutic strategy.
Zhang et al. (Mon,) studied this question.