IR@PKUHSC  > 北京大学第二临床医学院
学科主题临床医学
Endothelial Gab1 deficiency aggravates splenomegaly in portal hypertension independent of angiogenesis
Jiang, Beibei1; Deng, Qiuping1; Huo, Yingqing1; Li, Wei2; Shibuya, Masabumi3; Luo, Jincai1
关键词Gab1 portal hypertension splenomegaly
刊名AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
2015-03-01
DOI10.1152/ajpgi.00292.2014
308期:5页:G416-G426
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology ; Physiology
研究领域[WOS]Gastroenterology & Hepatology ; Physiology
关键词[WOS]NITRIC-OXIDE SYNTHASE ; PROTEIN-KINASE-A ; HYPERDYNAMIC SPLANCHNIC CIRCULATION ; GROWTH-FACTOR RECEPTORS ; INDUCED LIVER FIBROSIS ; KRUPPEL-LIKE FACTOR-2 ; SHEAR-STRESS ; SIGNAL-TRANSDUCTION ; SPLEEN ENLARGEMENT ; CIRRHOTIC RATS
英文摘要

Certain pathological changes, including angiogenesis, actively contribute to the pathogenesis of splenomegaly in portal hypertension (PH), although the detailed molecular and cellular mechanisms remain elusive. In this study, we demonstrated that endothelial Grb-2-associated binder 1 (Gab1) plays a negative role in PH-associated splenomegaly independent of angiogenesis. PH, which was induced by partial portal vein ligation, significantly enhanced Gab1 expression in endothelial cells in a time-dependent manner. Compared with controls, endothelium-specific Gab1 knockout (EGKO) mice exhibited a significant increase in spleen size while their PH levels remained similar. Pathological analysis indicated that EGKO mice developed more severe hyperactive white pulp and fibrosis in the enlarged spleen but less angiogenesis in both the spleen and mesenteric tissues. Mechanistic studies showed that the phosphorylation of endothelial nitric oxide synthase ( eNOS) in EGKO mice was significantly lower than in controls. In addition, the dysregulation of fibrosis and inflammation-related transcription factors [e.g., Kruppel-like factor (KLF) 2 and KLF5] and the upregulation of cytokine genes (e.g., TNF-alpha and IL-6) were observed in EGKO mice. We thus propose that endothelial Gab1 mediates multiple pathways in inhibition of the pathogenesis of splenomegaly in PH via prevention of endothelial dysfunction and overproduction of proinflammatory/profibrotic cytokines.

语种英语
WOS记录号WOS:000350817100006
Citation statistics
Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59102
Collection北京大学第二临床医学院
作者单位1.Peking Univ, Inst Mol Med, Lab Vasc Biol, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China
2.Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China
3.Jobu Univ, Inst Physiol & Med, Takasaki, Gumma, Japan
Recommended Citation
GB/T 7714
Jiang, Beibei,Deng, Qiuping,Huo, Yingqing,et al. Endothelial Gab1 deficiency aggravates splenomegaly in portal hypertension independent of angiogenesis[J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY,2015,308(5):G416-G426.
APA Jiang, Beibei,Deng, Qiuping,Huo, Yingqing,Li, Wei,Shibuya, Masabumi,&Luo, Jincai.(2015).Endothelial Gab1 deficiency aggravates splenomegaly in portal hypertension independent of angiogenesis.AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY,308(5),G416-G426.
MLA Jiang, Beibei,et al."Endothelial Gab1 deficiency aggravates splenomegaly in portal hypertension independent of angiogenesis".AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY 308.5(2015):G416-G426.
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