C1qRp/CD93 是一個表現在單核球細胞、嗜中性球細胞、內皮細胞以及幹細胞表面的高度醣基化蛋白質。CD93在巨噬細胞表面上無法偵測到；相反的，CD93 顯著的表現在血管內皮細胞層。序列比對顯示 CD93 與凝血酶調節素 (thrombomodulin) 在老鼠與人類中皆有很高的結構同源性，而且同屬於第一類型的穿膜蛋白。人類的 CD93 原先被視為 C1q 的細胞表面接受器，而且在活體外的實驗中，針對 CD93 的抗體可以抑制 C1q 依存性的吞噬作用。然而，在活體外的實驗中並沒有清楚的證據可以證明 C1q 和 CD93 之間的直接交互作用；而且在 CD93 缺失的老鼠中，吞噬作用的能力並沒有損壞。因此， CD93 參與在吞噬作用中的功能仍然是有爭議的。最近的研究已經證明了在血液中可偵測到可溶性的 CD93 存在，表示可溶性的 CD93 也許會參與調控某些生理作用。在本研究中，製備 CD93 的重組蛋白以研究其功能。以酵母菌表現系統表現五個表皮生長因子區域 epidermal growth factor (EGF)-like domains (CD93D2), 和五個表皮生長因子區域以及黏液素區域 (EGF with mucin-like domain, CD93D23) 的重組蛋白；而以哺乳動物細胞表現系統再表現 CD93D23 與 CD93的細胞外區域 (extracellular domain of CD93, CD93D123) 的重組蛋白。CD93D2, CD93D23 以及 CD93D123 對於人類臍帶靜脈內皮細胞 (HUVECs) 的生長與移動有刺激的作用。LY294002 與 U0126 可以抑制由 CD93D23 所誘發的 HUVECs 移動現象。我們發現由CD93D23 是經由將 FAK，ERK，PI3K/AKT/eNOS 磷酸化而引發 HUVECs 的趨化作用。以 CD93D23 處理HUVECs 可以刺激間質金屬結合蛋白酶-2 (matrix metalloproteinase-2, MMP-2) 和間質金屬結合蛋白酶-9 (MMP-9) 的產生。在小鼠的血管新生實驗中， CD93D23 可以刺激活體中的血管新生。這些結果顯示 CD93 的重組蛋白可以刺激 HUVECs 的生長、移動、間質金屬結合蛋白酶的製造，以及在活體中引起血管新生，暗示著 CD93 也許是一個促進血管生長的因子。

C1qRp/CD93 is a highly glycosylated protein expressed on monocytes, neutrophils, endothelial cells, and stem cells. CD93 is not detected on the surface of macrophage, which is a major kind of phagocytic cells; instead, it is markedly expressed on endothelium. Sequence alignment reveals that CD93 shares similar structural homology to thrombomodulin both in human and murine and belongs to type I transmembrane protein. Human CD93 was originally identified as a cell surface receptor of C1q, and certain antibodies directed against CD93 inhibited the C1q-dependent phagocytosis in vitro. However, there is no clear evidence of direct interaction between C1q and CD93 in vitro, and there is no impairment in phagocytic ability of CD93-deficient mice. Consequently, the role of CD93 involved in phagocytosis remained controversial. Recent study has demonstrated that soluble CD93 is detected in human plasma indicating that soluble CD93 might participate in some physiological processes. In this study, CD93 recombinant proteins were prepared to investigate their functions. CD93 recombinant proteins including five epidermal growth factor (EGF)-like domains (CD93D2), five EGF-like domains with a mucin-like domain (CD93D23) were expressed by Pichia pastoris expression system to investigate its functions; another CD93D23 and whole extracellular region (CD93D123) were expressed with human embryonic kidney cell (HEK-293)-based mammalian expression system. CD93D2, CD93D23, and CD93D123 had stimulatory effects on proliferation and migration of human umbilical vein endothelial cells (HUVECs). LY294002 (PI3K inhibitor) and U0126 (MEK ihibitor) inhibited CD93D23-induced HUVECs migration. We found that CD93D23 exhibited chemotactic activity on HUVECs through phosphorylation of focal adhesion kinase (FAK), extracellular signal-regulated kinase 1/2 (ERK), and phosphatidylinositol-3 kinase/ Akt/ endothelial nitric oxide synthase (eNOS). HUVECs incubated with CD93D23 up-regulated MMP2 and MMP9 production. In murine angiogenesis assay, CD93D23 stimulated angiogenesis in vivo. These results showed that recombinant CD93 could enhance HUVECs proliferation, migration, MMP production, and induce angiogenesis in vivo, implicating that soluble CD93 might be a pro-angiogenic factor.

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