钙黏蛋白 1 抵抗低氧诱导的人真皮淋巴管内皮细胞管形成抑制。
CEACAM1 resists hypoxia-induced inhibition of tube formation of human dermal lymphatic endothelial cells.
机构信息
Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
出版信息
Cell Signal. 2018 May;45:145-152. doi: 10.1016/j.cellsig.2018.02.005. Epub 2018 Feb 7.
Tube formation is one of the fundamental events required by angiogenesis and lymphangiogenesis. To date, there is little knowledge on the effects of hypoxia on tube formation of human dermal lymphatic endothelial cells (HDLECs). In this study, we found that tube formation of HDLECs was inhibited under hypoxic condition with decreased expressions of VEGF-D, CEACAM1 and Prox1 genes. However, hypoxia-induced inhibition of tube formation of HDLECs was reversed by conditional media from hypoxic tumor cells. After knockdown of CEACAM1 by siRNA transfection, tube formation of HDLECs was increased with elevated Prox1 expression, suggesting that CEACAM1 downregulates Prox1 and plays an inhibitory role in tube formation of HDLECs. Since the expressions of CEACAM1 and Prox1 were both decreased by hypoxia, there are additional mechanisms downregulating Prox1 expressions during hypoxia-inhibited tube formation of HDLECs.
管腔形成是血管生成和淋巴管生成所必需的基本事件之一。迄今为止，人们对缺氧对人皮肤淋巴管内皮细胞（HDLEC）管腔形成的影响知之甚少。在这项研究中，我们发现 HDLEC 的管腔形成在缺氧条件下受到抑制，VEGF-D、CEACAM1 和 Prox1 基因的表达降低。然而，缺氧诱导的 HDLEC 管腔形成抑制可被缺氧肿瘤细胞的条件培养基逆转。用 siRNA 转染敲低 CEACAM1 后，HDLEC 的管腔形成增加，Prox1 表达升高，表明 CEACAM1 下调 Prox1 并在 HDLEC 的管腔形成中发挥抑制作用。由于 CEACAM1 和 Prox1 的表达均受缺氧下调，因此在缺氧抑制 HDLEC 管腔形成过程中存在其他下调 Prox1 表达的机制。
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