Role of vascular endothelial growth factor in angiodysplasia: An interventional study with thalidomide

被引:24
|
作者
Tan, Honghong [1 ]
Chen, Huimin [1 ]
Xu, Chunhong [1 ]
Ge, Zhizheng [1 ]
Gao, Yunjie [1 ]
Fang, Jingyuan [1 ]
Liu, Wenzhong [1 ]
Xiao, Shudong [1 ]
机构
[1] Shanghai Jiao Tong Univ, State Key Lab Oncogene & Related Genes, Key Lab Gastroenterol & Hepatol,Minist Hlth, Sch Med,Renji Hosp,Shanghai Inst Digest Dis,GI Di, 145 Middle Shandong Rd, Shanghai 200001, Peoples R China
关键词
angiodysplasia; basic fibroblast growth factor; hypoxia-inducible factor-1; thalidomide; vascular endothelial growth factor; HYPOXIA-INDUCIBLE FACTOR-1; ANGIOGENESIS; EXPRESSION; CELLS;
D O I
10.1111/j.1440-1746.2011.06967.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background and Aim: The pathogenesis of angiodysplasia is still not fully understood and effective therapy is not available. Thalidomide was reported to be effective in the treatment of angiodysplasia, but the mechanisms underlying its activity are, as yet, unknown. We aimed to investigate the expression of vascular endothelial growth factor (VEGF) in angiodysplasia tissues, and the role of hypoxia-inducible factor-1a (HIF-1a) and basic fibroblast growth factor (bFGF) on VEGF expression in human umbilical vein endothelial cells (HUVEC). Additionally, we aimed to study the role of thalidomide in these parameters. Methods: Immunohistochemistry was performed to visualize VEGF in angiodysplasia lesions. HUVEC were incubated under hypoxic conditions or in the presence of bFGF. Effects of exposure to thalidomide were studied. Cell growth was assessed in methylthiazolyte-trazolium assays. Enzyme-linked immunosorbent assays and real-time polymerase chain reaction were performed to assess the expression of VEGF at protein and mRNA levels. Western blot was performed to detect the expression of HIF-1a under hypoxic conditions. Results: VEGF was strongly expressed in 75% of patients with angiodysplasia lesions, as compared to expression in patients without angiodysplasia lesions. VEGF was also induced in HUVEC under hypoxic conditions (P < 0.05). bFGF was found to stimulate the proliferation of HUVEC and enhance the expression of VEGF. Thalidomide suppressed bFGF-induced proliferation significantly and decreased VEGF expression, both at the protein and mRNA levels. Thalidomide also inhibited HIF-1a in a dose-dependent manner (P < 0.05). Conclusions: VEGF may play an important role in the pathogenesis of angiodysplasia. Thalidomide can suppress VEGF, either induced by HIF-1a or bFGF.
引用
收藏
页码:1094 / +
页数:112
相关论文
共 50 条
  • [1] Increased plasma vascular endothelial growth factor levels in patients with angiodysplasia
    Fujita, H
    Momoi, M
    Chuganji, Y
    Tomiyama, J
    [J]. JOURNAL OF INTERNAL MEDICINE, 2000, 248 (03) : 268 - 269
  • [2] Thalidomide inhibits angiogenesis induced by vascular endothelial growth factor
    Joussen, AM
    Kruse, FE
    Becker, M
    Rohrschneider, K
    Volcker, HE
    [J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 1997, 38 (04) : 1680 - 1680
  • [3] Role of vascular endothelial growth factor and vascular endothelial growth factor receptors in vascular development
    Carmeliet, P
    Collen, D
    [J]. VASCULAR GROWTH FACTORS AND ANGIOGENESIS, 1999, 237 : 133 - 158
  • [4] Vascular endothelial growth factor (VEGF) in patients with gastrointestinal (GI) angiodysplasia.
    Junquera, F
    Saperas, E
    Mourelle, M
    Malagelada, JR
    [J]. GASTROENTEROLOGY, 1997, 112 (04) : A374 - A374
  • [5] Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth factor
    Kruse, FE
    Joussen, AM
    Rohrschneider, K
    Becker, MD
    Volcker, HE
    [J]. GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 1998, 236 (06) : 461 - 466
  • [6] Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth factor
    F. E. Kruse
    Antonia M. Joussen
    Klaus Rohrschneider
    Matthias D. Becker
    Hans E. Völcker
    [J]. Graefe's Archive for Clinical and Experimental Ophthalmology, 1998, 236 : 461 - 466
  • [7] Role of vascular endothelial growth factor in keloids: a clinicopathologic study
    Salem, Ahmed
    Assaf, Magda
    Helmy, Afaf
    Nofal, Ahmad
    Ibrahim, Samia
    Eldeeb, Fatma
    Youssef, Christeen
    [J]. INTERNATIONAL JOURNAL OF DERMATOLOGY, 2009, 48 (10) : 1071 - 1077
  • [8] The role of vascular endothelial growth factor in ossification
    Ricky Wong
    Alex Wenden
    A Bakr M Rabie
    [J]. International Journal of Oral Science, 2012, 4 (02) : 64 - 68
  • [9] The role of vascular endothelial growth factor in angiogenesis
    Maruotti, Nicola
    Ribatti, Domenico
    [J]. SALUD I CIENCIA, 2008, 16 (04): : 383 - 386
  • [10] The role of vascular endothelial growth factor in ossification
    Yang, Yan-Qi
    Tan, Ying-Ying
    Wong, Ricky
    Wenden, Alex
    Zhang, Lin-Kun
    Rabie, A. Bakr M.
    [J]. INTERNATIONAL JOURNAL OF ORAL SCIENCE, 2012, 4 (02) : 64 - 68