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肝脏发育过程中血管生成控制因子的调节:色素上皮衍生因子在正常脉管系统形成和维持中的作用

Regulation of factors controlling angiogenesis in liver development: a role for PEDF in the formation and maintenance of normal vasculature.

作者信息

Sawant S, Aparicio S, Tink A R, Lara N, Barnstable C J, Tombran-Tink J

机构信息

Pharmaceutical Sciences, University of Missouri Kansas City, Kansas City, MO, USA.

出版信息

Biochem Biophys Res Commun. 2004 Dec 10;325(2):408-13. doi: 10.1016/j.bbrc.2004.10.041.

DOI:10.1016/j.bbrc.2004.10.041
PMID:15530407
Abstract

PEDF and VEGF are important inhibitors and promoters of angiogenesis, and the ratio between the two is an important indicator in many neovascular diseases. In mouse liver PEDF and VEGF(165) were co-expressed at very early stages of liver development and their expression increased as liver embryogenesis progressed, suggesting that PEDF and VEGF are both crucial to vasculogenesis as well. VEGF(189) only appears at the P0 stage in liver organogenesis and is maintained at high levels thereafter. PEDF and the two VEGF isoforms are synthesized by fresh and cultured hepatocytes. Expression of VEGF(121) and overexpression of VEGF(165) were only seen in HepG2, a well-characterized hepatocellular carcinoma line. The results suggest that hepatic vascular architecture is under the control of both PEDF and VEGF, and that VEGF(165) and VEGF(189) have distinct functions in normal vascular development of the liver. The VEGF isoforms 121 and 189 may be key regulators of increased vascularity and progression of hepatocellular carcinoma, one of the most common malignant tumors, and may be of prognostic significance for this tumor.

摘要

色素上皮衍生因子(PEDF)和血管内皮生长因子(VEGF)是血管生成的重要抑制剂和促进剂,二者之间的比例是许多新生血管疾病的重要指标。在小鼠肝脏中,PEDF和VEGF(165)在肝脏发育的早期阶段共同表达,并且随着肝脏胚胎发生的进展其表达增加,这表明PEDF和VEGF对血管发生也都至关重要。VEGF(189)仅在肝脏器官发生的P0阶段出现,此后维持在高水平。PEDF和两种VEGF异构体由新鲜的和培养的肝细胞合成。VEGF(121)的表达和VEGF(165)的过表达仅在HepG2(一种特征明确的肝癌细胞系)中可见。结果表明,肝脏血管结构受PEDF和VEGF的共同控制,并且VEGF(165)和VEGF(189)在肝脏正常血管发育中具有不同的功能。VEGF异构体121和189可能是最常见的恶性肿瘤之一肝细胞癌血管增多和进展的关键调节因子,并且可能对该肿瘤具有预后意义。

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