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- W4319433520 abstract "Abstract Monocytes and macrophages (Mo/Mφ) play critical roles in all phases of normal skin wound healing. However, persistent accumulation of pro-inflammatory Mo/Mφ contributes to impaired healing in diabetes. The purpose of this study was to determine whether proliferation contributes to Mo/Mφ accumulation in skin wounds. First, proliferating Mo/Mφ (F4/80+Ki67+) were observed in wound cryosections from non-diabetic mice. Next, cell cycle analysis indicated skin wounding increased the number and percentage of Ly6C+F4/80lo/-Mo/Mφ in the S/G2/M phases peaking on day 6 post-wounding with significantly more proliferating cells in wounds from diabetic mice compared to non-diabetic mice. Moreover, unbiased scRNAseq analysis revealed that a cluster dominantly composed of wound Mo/Mφ from diabetic mice exhibited upregulation of genes associated with progression and regulation of cell cycle. Finally, a screen of potential regulators of wound Mo/Mφ proliferation showed increased wound CCL2 levels in diabetic versus non-diabetic mice and that local treatment with CCL2 protein increased proliferation of wound Ly6C+F4/80lo/-Mo/Mφ in non-diabetic mice. Importantly, adoptive transfer of mixtures of CCR2−/− and CCR2+/+ Ly6Chi Mo suggested a critical role for CCL2/CCR2 signaling in promoting Mo/Mφ proliferation in the wound environment. Together, these data demonstrate 1) Ly6C+/F4/80lo/-Mo/Mφ proliferate during skin wound healing with higher rates in wounds from diabetic mice than non-diabetic mice and, 2) a novel role for the CCL2/CCR2 signaling pathway in promoting skin Mo/Mφ proliferation, contributing to persistent accumulation of Mo/Mφ and impaired healing in diabetic mice." @default.
- W4319433520 created "2023-02-09" @default.
- W4319433520 creator A5001167767 @default.
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- W4319433520 date "2021-05-01" @default.
- W4319433520 modified "2023-09-23" @default.
- W4319433520 title "Proliferation of Ly6C+ monocytes/macrophages contributes to their accumulation and inflammation in mouse skin wound healing" @default.
- W4319433520 doi "https://doi.org/10.4049/jimmunol.206.supp.111.01" @default.
- W4319433520 hasPublicationYear "2021" @default.
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