PT - JOURNAL ARTICLE AU - Lothstein, Katherine E AU - Chen, Fei AU - Mishra, Pankaj AU - Smyth, Danielle J AU - Wu, Wenhui AU - Lemenze, Alexander AU - Kumamoto, Yosuke AU - Maizels, Rick M AU - Gause, William C TI - Helminth protein enhances wound healing by inhibiting fibrosis and promoting tissue regeneration AID - 10.26508/lsa.202302249 DP - 2024 Nov 01 TA - Life Science Alliance PG - e202302249 VI - 7 IP - 11 4099 - https://www.life-science-alliance.org/content/7/11/e202302249.short 4100 - https://www.life-science-alliance.org/content/7/11/e202302249.full SO - Life Sci. Alliance2024 Nov 01; 7 AB - Skin wound healing due to full thickness wounds typically results in fibrosis and scarring, where parenchyma tissue is replaced with connective tissue. A major advance in wound healing research would be to instead promote tissue regeneration. Helminth parasites express excretory/secretory (ES) molecules, which can modulate mammalian host responses. One recently discovered ES protein, TGF-β mimic (TGM), binds the TGF-β receptor, though likely has other activities. Here, we demonstrate that topical administration of TGM under a Tegaderm bandage enhanced wound healing and tissue regeneration in an in vivo wound biopsy model. Increased restoration of normal tissue structure in the wound beds of TGM-treated mice was observed during mid- to late-stage wound healing. Both accelerated re-epithelialization and hair follicle regeneration were observed. Further analysis showed differential expansion of myeloid populations at different wound healing stages, suggesting recruitment and reprogramming of specific macrophage subsets. This study indicates a role for TGM as a potential therapeutic option for enhanced wound healing.All data are available in the main text or the supplementary materials. scRNAseq data were deposited into the Gene Expression Omnibus database under the accession number GSE272815.