Expression of Angiopoietins and Angiogenic Signaling Pathway Molecules in Chronic Subdural Hematomas
Expression of Angiopoietins and Angiogenic Signaling Pathway Molecules in Chronic Subdural Hematomas
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DOI：
10.1089/neu.2020.7042
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发表时间：
2020-06-26
影响因子：
4.2
通讯作者：
Miyachi, Shigeru
中科院分区：
文献类型：
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作者：
Isaji, Taiki;Osuka, Koji;Miyachi, Shigeru
慢性硬膜下血肿（CSDH）是一种与多种炎症介质有关的血管生成性疾病。Tie 2主要在胚胎内皮中表达，并在血管系统的成熟和稳定中起重要作用。血管生成素（Ang）1和Ang 2是熟知的Tie 2受体的配体。我们检测了CSDH液中Ang 1和Ang 2的表达以及CSDH外膜中Tie-2受体和血管生成信号通路组分的表达。共采集25份CSDH液和8份CSDH外膜。采用酶联免疫吸附试验（ELISA）检测CSDH液中Ang 1和Ang 2的浓度。通过蛋白质印迹分析检测Tie 2、磷酸肌醇3-激酶（PI 3 K）、蛋白激酶B（Akt）雷帕霉素的机械靶点（mTOR）、G β L、70 kDa核糖体蛋白S6激酶（p70 S6 K）、真核起始因子4 E（eIF-4 E）和β-肌动蛋白的表达。免疫组化检测Tie 2、Akt和mTOR的表达。CSDH液中Ang 2的浓度显著高于血清和脑脊液（CSF）中Ang 2的浓度，也高于CSDH液中Ang 1的浓度。Tie 2、PI 3 K、Akt、mTOR、G β L、p70 S6 K和eIF-4 E在所有病例中均检测到。此外，Tie 2、Akt和mTOR定位于CSDH外膜中的血管内皮细胞中。我们的数据表明，CSDH液体中的Ang 2（而不是Ang 1）通过Tie 2受体促进内皮细胞的血管生成。因此，Ang 2/Tie 2信号通路可能是治疗顽固性CSDH生长的有用的治疗靶点。
Chronic subdural hematoma (CSDH) is an angiogenic disease that is involved with many inflammatory mediators. Tie2 is predominantly expressed in the embryonic endothelium and plays an important role in the maturation and stabilization of the vasculature. Angiopoietin (Ang)1 and Ang2 are well-known ligands of the Tie2 receptor. We examined the expression of Ang1 and Ang2 in CSDH fluid and the expression of Tie-2 receptor and components of the angiogenic signaling pathways in the outer membrane of CSDH. Twenty-five samples of CSDH fluid and eight samples of outer membrane of CSDH were included. The concentrations of Ang1 and Ang2 in the CSDH fluid were measured using enzyme-linked immunosorbent assay (ELISA) kits. The expression of Tie2, phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) mechanistic target of rapamycin (mTOR), G beta L, 70 kDa ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E (eIF-4E), and beta-actin was examined by a Western blot analysis. The expression of Tie2, Akt, and mTOR was also examined by immunohistochemistry. The concentration of Ang2 in CSDH fluid was significantly higher than that in the serum or cerebrospinal fluid (CSF), and also higher than that of Ang1 in CSDH fluid. Tie2, PI3K, Akt, mTOR, G beta L, p70S6K, and eIF-4E were detected in all cases. In addition, Tie2, Akt, and mTOR were localized in the endothelial cells of vessels in the CSDH outer membrane. Our data suggest that Ang2, although not Ang1, in CSDH fluid promotes angiogenesis in endothelial cells through the Tie2 receptor. The Ang2/Tie2 signaling pathway might therefore be a useful therapeutic target for treating the growth of intractable CSDH.