Granulocyte colony stimulating factor promotes scarless tissue regeneration.

IF 6.9 1区 生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2024-10-22 Epub Date: 2024-09-21 DOI:10.1016/j.celrep.2024.114742
Jianhe Huang, Satish Sati, Christina Murphy, Casey A Spencer, Emmanuel Rapp, Stephen M Prouty, Scott Korte, Olivia Ahart, Emily Sheng, Parker Jones, Anna E Kersh, Denis Leung, Thomas H Leung
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Abstract

Mammals typically heal with fibrotic scars, and treatments to regenerate human skin and hair without a scar remain elusive. We discovered that mice lacking C-X-C motif chemokine receptor 2 (CXCR2 knockout [KO]) displayed robust and complete tissue regeneration across three different injury models: skin, hair follicle, and cartilage. Remarkably, wild-type mice receiving plasma from CXCR2 KO mice through parabiosis or injections healed wounds scarlessly. A comparison of circulating proteins using multiplex ELISA revealed a 24-fold higher plasma level of granulocyte colony stimulating factor (G-CSF) in CXCR2 KO blood. Local injections of G-CSF into wild-type (WT) mouse wound beds reduced scar formation and increased scarless tissue regeneration. G-CSF directly polarized macrophages into an anti-inflammatory phenotype, and both CXCR2 KO and G-CSF-treated mice recruited more anti-inflammatory macrophages into injured areas. Modulating macrophage activation states at early time points after injury promotes scarless tissue regeneration and may offer a therapeutic approach to improve healing of human skin wounds.

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粒细胞集落刺激因子可促进无疤痕组织再生。
哺乳动物痊愈后通常会留下纤维化疤痕,而无疤痕再生人类皮肤和毛发的治疗方法仍未出现。我们发现,在皮肤、毛囊和软骨这三种不同的损伤模型中,缺乏 C-X-C 矩阵趋化因子受体 2(CXCR2 基因敲除 [KO])的小鼠表现出强大而完整的组织再生能力。值得注意的是,野生型小鼠通过同种异体移植或注射 CXCR2 KO 小鼠的血浆后,伤口愈合后不留疤痕。使用多重酶联免疫吸附法对循环蛋白进行比较后发现,CXCR2 KO 小鼠血液中的粒细胞集落刺激因子(G-CSF)的血浆水平高出 24 倍。向野生型(WT)小鼠伤口床局部注射 G-CSF 可减少疤痕的形成并增加无疤痕组织的再生。G-CSF 直接将巨噬细胞极化为抗炎表型,CXCR2 KO 和 G-CSF 处理过的小鼠都将更多的抗炎巨噬细胞募集到受伤区域。在损伤后的早期阶段调节巨噬细胞的活化状态可促进无疤痕组织的再生,并为改善人类皮肤伤口的愈合提供了一种治疗方法。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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