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成年斑马鱼皮肤伤口愈合过程中周细胞对血管生成的调节作用

Pericyte-mediated regulation of angiogenesis during cutaneous wound healing in adult zebrafish.

作者信息

Ishii Tomohiro, Yuge Shinya, Ando Koji, Zhou Weibin, Fukuhara Shigetomo

机构信息

Department of Molecular Pathophysiology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, Japan.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Commun Biol. 2025 Jul 25;8(1):1101. doi: 10.1038/s42003-025-08517-7.

Abstract

Pericytes are mural cells that wrap small caliber vessels, playing a crucial role in stabilizing vascular structure. Upon induction of angiogenesis, pericytes were thought to detach from the vessel wall, thereby facilitating the sprouting of endothelial cells (ECs). However, the precise roles of pericytes in regulating angiogenesis still remain elusive. Here, we demonstrate, by performing live-imaging of adult zebrafish, that pericytes actively regulate angiogenesis during wound healing. We generated a zebrafish line which enables the conditional ablation of mural cells, including pericytes, and analyzed cutaneous wound angiogenesis. Loss of pericytes significantly increased the number of sprouting events of ECs and promoted their proliferation, resulting in the formation of dense and disorganized blood vessel networks. Furthermore, in the absence of pericytes, the injured vessels showed abnormal vessel elongation, thereby generating ectopic vascular networks. These results suggest that pericytes play an active role for generating functional blood vessels during wound angiogenesis.

摘要

周细胞是包裹小口径血管的壁细胞,在稳定血管结构中起关键作用。在血管生成诱导时,周细胞被认为会从血管壁脱离,从而促进内皮细胞(ECs)的芽生。然而,周细胞在调节血管生成中的精确作用仍然难以捉摸。在此,我们通过对成年斑马鱼进行实时成像证明,周细胞在伤口愈合过程中积极调节血管生成。我们构建了一个斑马鱼品系,能够有条件地消融包括周细胞在内的壁细胞,并分析皮肤伤口血管生成。周细胞的缺失显著增加了内皮细胞的芽生事件数量并促进其增殖,导致形成密集且紊乱的血管网络。此外,在没有周细胞的情况下,受伤血管显示出异常的血管伸长,从而产生异位血管网络。这些结果表明,周细胞在伤口血管生成过程中对生成功能性血管起积极作用。

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