皮膚・軟部組織が損傷・欠損すると, これを復元すべく内因性の創傷治癒機構が発動する。その過程において中心的な役割を果たすのが周囲の血管からのいわゆる「血管新生」であると考えられている。本研究では, この創傷治癒における血管の変動を, 従来の「血管新生」の枠組みにとどまらず, より包括的に「創傷血管網リモデリング」と称し, その全容の解明を目的として遂行された。その結果, 創傷血管網リモデリングの主体は, 血管の増殖や分枝増加よりむしろ, 血管径の増大や血流増加, 創収縮に伴う血管の方向性の変化であり, 特に前2者については, 各種変異マウスの解析により, VEGF/VEGFR2シグナルに依存していることをつきとめた。
Once skin tissues are injured, the endogenous healing program takes place and damaged tissues are repaired or regenerated. Angiogenesis, formation of new blood vessels from nascent vessels, are believed to play a central role in this repairing process. However, the entity of the kinetics of blood vessels associated with wound healing is only ambiguously clarified. Here we established a new wound healing model using neonatal mice, suitable for visualizing the 3-D structure of blood vessels in wound tissues. Utilizing this technique, we found vascular changes during wound repair are mainly the vascular enlargement accompanied by increased blood flow, and the vessel curving caused by wound contraction, rather than typical angiogenesis. We also found the increase in diameter and blood flow depends on the VEGF-VEGFR2 signaling. These results suggest the vascular remodeling during wound healing is not a typical angiogenesis, but uniquely characterized as enlargement and curving.
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