New Modes of GPCR Signalling

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TEF3(Transcription Enhancer Factor 3)Induced Angiogenesis through VEGF Pathway Xin Liu1, Cheng Qiao1, and Dezheng Zhao2,4 Huiyan Zeng2,3,4*, 1.Department of Microbiological and Biochemical Pharmacy, College of Pharmacy , Wuhan University, Wuhan 430071, PR China 2 .Departments of Pathologyand Medicine (Division of Molecular & Vascular Medicine), 3. Center for vascular Biology Research 4.Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA 02215, USA Aims: Transcription Enhancer Factor-3 (TEF3, RTEF-1, TEAD4) belongs to a family of transcription factor proteins. Although it has been extensively studied, the signaling pathways mediating its biological functions during angiogenensis are still not understood. Recently we identified a novel VEGF targeted gene, Down Syndrome Candidate Region 1 isoform 1L (DSCR1-1L) that is important for the function of VEGF in pathological angiogenesis and is expressed in human tumor vasculature, not in normal vasculature, rendering it a specific target for tumor angiogenesis therapy. TEF3 was required for DSCR1-1L expression through binding to the M-CAT site in its promoter and could be an attractive target for anti-angiogenesis therapy. It was also reported that TEF3 expression is induced by hypoxia and TEF3 overexpression increases VEGF gene transcription and in vitro under hypothexia condition. Ours aims are to investigate the role of TEF3 in angiogenesis. Methods: We overexpressed TEF3 in HUVEC cell and we used the yeast two-hybrid system to find the proteins interaction with the TEF3. Results: We reported previously that another DSCR1 isoform, DSCR1-1L, was also upregulated by VEGF-A 165 in cultured endothelial cells and in several in vivo models of pathological angiogenesis and that different from DSCR1-4, DSCR1-1L overexpression alone induced cultured endothelial cell proliferation and promoted angiogenesis in Matrigel assays. We also demonstrated that TEF3 directly interacted with the putative M-CAT site in the DSR1-1L promoter in vitro and in vivo. Finally, Overexpression of TEF3 induces HUVEC proliferation, migration and tube formation. Conclusion: TEF3 upregulatecd DSCR1-1l expression with the VEGF stimulation,and TEF3 itself can promote angiogenesis in endothelial cells. Then it was tested that TEF3 also acts as a novel factor in VEGF-induced angiogenesis signaling pathway. Key Words: VEGF; TEF3; angiogenesis Authors: Xin Liu ,Email: lx@whu.edu.cn; Huiyan Zeng, Email: hzeng@caregroup.harvard.edu Tel: 86-27-68759006
Does the Metabotropic Glutamate Receptor 7 (Mglur7) Play a Role in Schizophrenia? Yali Zhao, Yu Fan, Qi Xu*, Yan Shen* National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University. No. 5, Dong Dan San Tiao, Beijing, China, 100005 Background: The metabotropic glutamate receptor 7 (mGluR7) is a class C G-protein coupled receptor found in the pre-synaptic elements of various types of neurons, which plays a critical role in regulating the glutamate transmission. Glutamate is the predominant excitatory neurotransmitter in the central nervous system. Glutamate blocking drugs such as phencyclidine can mimic the psychosis symptoms and cognitive problems associated with schizophrenia, which is a common yet severe psychiatric disorder and characterized by hallucinations, delusions and cognitive deficits with a lifetime risk of about 1%. Aim: The purpose of this study is to investigate the contribution of mGluR7 to schizophrenia susceptibility. We genotyped 14 single nucleotide polymorphisms (SNPs) located in the functional region of mGluR7 among 549 patients with schizophrenia and 562 controls origining from Chinese utilizing Sequenom MassARRAY iPLEX Gold platform (Sequenom, San Diego, California). The differences of allelic and genotypic frequencies between patients and controls were examined using Unphased software (v 3.0.12). Results: We observed no significant allelic associations with the disease in any of the 14 SNPs. We also observed no significant genotypic differences between patients and controls. Conclusion: These results suggested that mGluR7 may not play a major role in schizophrenia pathogenesis in the Chinese population as it is a multifactor disease. Key Words: metabotropic glutamate receptor 7; Glutamate; schizophrenia; Author: Yali Zhao, Tel: 86-10-65296432; Email: hollyzyl@126.com; Corresponding author: Qi Xu, Tel: 86-10-65296432; Email: qixu@vip.sina.com
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