Zinc Finger Protein St18 Protects against Septic Death by Inhibiting VEGF-A from Macrophages.

Cell Reports
Kenta MaruyamaYutaro Kumagai

Abstract

Zinc finger protein St18 was initially reported as candidate tumor suppressor gene, and also suggested that fibroblast St18 positively regulates NF-κB activation. Despite the pleiotropic functions of St18, little is known about its roles in macrophages. Here, we report that myeloid St18 is a potent inhibitor of VEGF-A. Mice lacking St18 in myeloid lineages exhibit increased retinal vasculature with enhanced serum VEGF-A concentrations. Despite the normal activation of NF-κB target genes, these mice are highly susceptible to LPS-induced shock, polymicrobial sepsis, and experimental colitis, accompanied by enhanced vascular and intestinal leakage. Pharmacological inhibition of VEGF signaling rescued the high mortality rate of myeloid-specific St18-deficient mice in response to inflammation. Mechanistically, St18 directly binds to Sp1 and attenuates its activity, leading to the suppression of Sp1 target gene VEGF-A. Using mouse genetic and pharmacological models, we reveal myeloid St18 as a critical septic death protector.

References

Apr 3, 1992·Science·D P CerrettiL A Cannizzaro
Jun 17, 1998·Arthritis and Rheumatism·A E Koch
Jan 6, 2000·Transgenic Research·B E ClausenI Förster
Jul 30, 2004·Genesis : the Journal of Genetics and Development·Fatima el MarjouSylvie Robine
Oct 19, 2004·Oncogene·Burkhard JandrigAndré Rosenthal
Dec 23, 2004·Shock·Michiel van der FlierSibyl P Geelen
Jan 11, 2005·Critical Care Medicine·Edward A PanacekUNKNOWN Monoclonal Anti-TNF: a Randomized Controlled Sepsis Study Investigators
Jan 25, 2005·Cardiovascular Research·Gilles Pagès, Jacques Pouysségur
Jul 16, 2005·Journal of Atherosclerosis and Thrombosis·Mika KobayashiTatsuhiko Kodama
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Apr 25, 2006·Nature Reviews. Molecular Cell Biology·Anna-Karin OlssonLena Claesson-Welsh
Apr 28, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel SteinbachBernd Gruhn
May 17, 2006·The Journal of Experimental Medicine·Kiichiro YanoWilliam C Aird
Aug 5, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Julia YangDana T Graves
Sep 25, 2008·American Journal of Physiology. Endocrinology and Metabolism·Sofianos AndrikopoulosJoseph Proietto
Nov 18, 2008·Gastroenterology·Franco ScaldaferriSilvio Danese
Dec 25, 2008·Nucleic Acids Research·Keishin NishidaKenta Nakai
Jul 25, 2009·Nature Reviews. Cancer·Erwin F Wagner, Angel R Nebreda
Feb 4, 2010·Molecular Biology of the Cell·Donald R Senger
Mar 23, 2010·Cell·Osamu Takeuchi, Shizuo Akira
Feb 19, 2011·Bioinformatics·Charles E GrantWilliam Stafford Noble
Apr 3, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dominic G HildebrandKlaus Schulze-Osthoff
Aug 30, 2013·The New England Journal of Medicine·Derek C Angus, Tom van der Poll
Feb 11, 2014·The Journal of Biological Chemistry·Cyndi HenryJean Buteau
Dec 17, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel SteinbachBernd Gruhn
Mar 24, 2016·Journal of Cell Science·Daisuke YamazakiHiroaki Miki
Jul 7, 2016·Mucosal Immunology·Kosuke FujimotoKiyoshi Takeda
Nov 20, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Micol RavàBruno Amati
Jan 7, 2017·World Journal of Gastroenterology : WJG·Yazan AbuodehGhassan El-Haddad
Feb 6, 2017·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Jakob SiedleckiKirsten Eibl-Lindner
Jun 8, 2017·The New England Journal of Medicine·Rebecca E BergerMitchell M Levy

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