The novel axis of YAP1, transcription enhancer factor 3 and Down Syndrome Candidate Region 1 isoform 1L is a common signaling pathway downstream of several angiogenic factors.

Autor: Cui P; Center for Vascular Biology Research and Division of Gastroenterology, Departments of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Pancreatic Disease Institute, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China., Liu X; Center for Vascular Biology Research and Division of Gastroenterology, Departments of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA., Zhao K; Center for Vascular Biology Research and Division of Gastroenterology, Departments of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA., Hou S; Center for Vascular Biology Research and Division of Gastroenterology, Departments of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Chen C; Center for Vascular Biology Research and Division of Gastroenterology, Departments of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Department of Surgery of Breast and Thyroid, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China., Zhao D; Center for Vascular Biology Research and Division of Gastroenterology, Departments of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA., Zeng H; Center for Vascular Biology Research and Division of Gastroenterology, Departments of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Electronic address: hzeng@bidmc.harvard.edu.
Jazyk: angličtina
Zdroj: Microvascular research [Microvasc Res] 2020 May; Vol. 129, pp. 103955. Date of Electronic Publication: 2019 Nov 13.
DOI: 10.1016/j.mvr.2019.103955
Abstrakt: Angiogenesis is a hallmark of many diseases. Previously, we found that Down Syndrome Candidate Region 1 Isoform 1L (DSCR1-1L) was expressed in human tumor vessels, but was not detectable in normal tissues, and played important roles in angiogenesis induced by vascular endothelial growth factor (VEGF-A 165 ). The expressions of DSCR1-1L mRNA and protein induced by VEGF-A 165 were regulated via the direct interaction of transcription enhancer factor 3 (TEF3) with DSCR1-1L promoter. However, the function and the regulation of DSCR1-1L in angiogenesis had not been completely understood. In this study, we found that the expressions of DSCR1-1L mRNA and proteins were upregulated by other angiogenic factors, including VEGF-A 121 , VEGF-E, histamine, PAF, the endothelial cell (EC) growth medium, and the conditional medium obtained from cancer cells, but not by PlGF, bFGF, PDGF, and serotonin. The EC proliferation, migration and elongation induced by histamine and EC growth medium were inhibited by knocking down the mRNA and protein expressions of DSCR1-1L and TEF3. The TEF3 activation was regulated by its interaction with YAP1, and translocation from cytosol to nuclei, but not by increase of protein expression, after the stimulation of VEGF, histamine and EC growth medium. YAP1 regulated the protein expression of DSCR1-1L, the proliferation, migration and elongation of ECs induced by VEGF, histamine and EC growth medium. Taken together, this study identified a novel axis of YAP1, TEF3 and DSCR1-1L that was a common signaling pathway downstream of several angiogenic factors to regulate angiogenesis, suggesting that this pathway is an excellent therapeutic target for angiogenic diseases and cancers. Our results contribute significantly to the field of mechanistic studies.
Competing Interests: Declaration of competing interest All authors claim no conflict of interest.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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