血管瘤是婴幼儿最常见的先天性良性肿瘤，快速增生期病变进展较快，引起严重的形态和功能障碍。现有研究及本课题组前期研究已证实增生期血管瘤中存在大量巨噬细胞，促进血管瘤快速发展。此外，本课题组前期实验发现：缺氧条件下，血管瘤干细胞可促进单核细胞和巨噬细胞的迁移、极性转换，且与转录因子ATF4和M-CSF/M-CSFR信号通路表达上调有关。本课题旨在研究M-CSF/M-CSFR信号通路在增生期血管瘤组织中对巨噬细胞浸润和极性转换的调控作用，并深入探讨局部缺氧微环境及ATF4在上述过程中的介导作用和具体分子机制；在此基础上以血管瘤裸鼠模型为实验对象，探讨靶向转录因子ATF4或M-CSF/M-CSFR信号通路抑制巨噬细胞浸润和极性转换、抑制血管生成在血管瘤治疗中的应用前景。本课题研究有助于开拓血管瘤治疗的新疗法，并可能为治疗其他病理性血管增生相关疾病提供新思路。

Infantile hemangiomas (IH) are the most common benign tumor of infancy, which are characterized by the rapid development in the proliferating phase and may result in the disfigurement and dysfunction. Previous studies have reported that macrophages are prevalent in the proliferating phase and play important roles in IH. In addition, our preliminary researches indicate that the hemangioma stem cells (HemSCs) could promote the migration and differentiation of monocytes or macrophages under hypoxic conditions, which may be due to the up-regulation of activating transcription factor 4 (ATF4) and M-CSF/M-CSFR signaling pathway. The aims of our project are as follows: (1) To uncover the roles of M-CSF/M-CSFR in the macrophage infiltration and polarization of IH; (2) To investigate the effects of hypoxia and ATF4 in the above process; (3) To explore the effects of ATF4- or M-CSF/M-CSFR-targeting strategy on the treatment of IH using the murine model of IH. Our project would be beneficial for developing novel remedy for IH or other angiogenesis-related diseases.