Department of Molecular Pathophysiology, Institute of Advanced Medical Sciences, Nippon Medical School, 1-396 Kosugi-machi, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan.
Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan.
Angiogenesis. 2019 May;22(2):341-354. doi: 10.1007/s10456-018-09660-y. Epub 2019 Jan 4.
Angiogenesis, the growth of new blood vessels from pre-existing vessels, is critical for cutaneous wound healing. However, it remains elusive how endothelial cells (ECs) and pericytes (PCs) establish new blood vessels during cutaneous angiogenesis. We set up a live-imaging system to analyze cutaneous angiogenesis in adult zebrafish. First, we characterized basic structures of cutaneous vasculature. In normal skin tissues, ECs and PCs remained dormant to maintain quiescent blood vessels, whereas cutaneous injury immediately induced angiogenesis through the vascular endothelial growth factor signaling pathway. Tortuous and disorganized vessel networks formed within a few weeks after the injury and subsequently normalized through vessel regression in a few months. Analyses of the repair process of injured single blood vessels revealed that severed vessels elongated upon injury and anastomosed with each other. Thereafter, repaired vessels and adjacent uninjured vessels became tortuous by increasing the number of ECs. In parallel, PCs divided and migrated to cover the tortuous blood vessels. ECs sprouted from the PC-covered tortuous vessels, suggesting that EC sprouting does not require PC detachment from the vessel wall. Thus, live imaging of cutaneous angiogenesis in adult zebrafish enables us to clarify how ECs and PCs develop new blood vessels during cutaneous angiogenesis.
血管生成，即从预先存在的血管中生长出新的血管，对于皮肤伤口愈合至关重要。然而，内皮细胞（ECs）和周细胞（PCs）如何在皮肤血管生成过程中建立新的血管仍然难以捉摸。我们建立了一个活体成像系统来分析成年斑马鱼的皮肤血管生成。首先，我们描述了皮肤脉管系统的基本结构。在正常皮肤组织中，ECs 和 PCs 处于休眠状态以维持静止的血管，而皮肤损伤通过血管内皮生长因子信号通路立即诱导血管生成。损伤后几周内，迂曲和紊乱的血管网络形成，随后在几个月内通过血管退化恢复正常。对单个受损血管修复过程的分析表明，受损的血管在损伤后伸长并相互吻合。此后，修复后的血管和相邻的未受损血管通过增加 EC 的数量变得迂曲。与此同时，PCs 分裂并迁移以覆盖迂曲的血管。ECs 从 PC 覆盖的迂曲血管中发芽，表明 EC 发芽不需要 PC 从血管壁上脱离。因此，成年斑马鱼皮肤血管生成的活体成像使我们能够阐明 ECs 和 PCs 在皮肤血管生成过程中如何发育新的血管。
