Helicobacter pyloristimulates hostvascular endothelial growth factor‐A(vegf‐A) gene expression via MEK/ERK‐dependent activation of Sp1 and Sp3
Open Access
- 3 November 2003
- journal article
- fj express-summarie
- Published by Wiley in The FASEB Journal
- Vol. 18 (1), 218-220
- https://doi.org/10.1096/fj.03-0055fje
Abstract
VEGF-A is a key regulator of inflammatory and tumor-associated angiogenesis. H. pylori plays a critical role in the pathogenesis of benign and malignant gastric diseases. It has been suggested that H. pylori infection is associated with activation of host angiogenesis, however, underlying mechanisms as well as angiogenic growth factors activated by the bacterium have not yet been identified. Therefore, we investigated the influence of the bacterium on VEGF-A as a candidate host target gene in vivo and in vitro. We show that H. pylori potently up-regulates production and release of VEGF-A protein as well as vegf-A mRNA levels, and we provide strong evidence that enhanced recruitment of Sp1 and Sp3 transcription factors to two proximal GC-rich vegf-A promoter elements mediates H. pylori-triggered vegf-A gene expression. In addition, H. pylori infection increased the transactivating capacity of both Sp1 and Sp3, which suggests additional mechanism(s) of vegf-A gene regulation by the bacterium. Signaling studies identified the MEK>ERK1/-2 kinase cascade as principal host signaling pathway mediating H. pylori-stimulated vegf-A transcription. By identifying H. pylori as potent activator of vegf-A gene expression and characterization of underlying molecular mechanisms, our results provide novel insights into pathways linking the bacterium to host angiogenesis and may help to develop strategies to influence vegf-A gene expression in the setting of H. pylori infection.Keywords
This publication has 42 references indexed in Scilit:
- Oxidative Stress Regulates Vascular Endothelial Growth Factor-A Gene Transcription through Sp1- and Sp3-dependent Activation of Two Proximal GC-rich Promoter ElementsJournal of Biological Chemistry, 2003
- Redox signaling in vascular angiogenesis1,2 1Guest Editor: Toshikazu Yoshikawa 2This article is part of a series of reviews on “Vascular Dysfunction and Free Radicals.” The full list of papers may be found on the homepage of the journal.Free Radical Biology & Medicine, 2002
- Molecular Profiling of Angiogenesis MarkersThe American Journal of Pathology, 2002
- B‐Raf/Rap1 signaling, but not c‐Raf‐1/Ras, induces the histidine decarboxylase promoter inHelicobacter pyloriinfectionThe FASEB Journal, 2002
- Helicobacter pylori and gastrointestinal tract adenocarcinomasNature Reviews Cancer, 2002
- Evidence of a leading role for VEGF inBartonella henselae-induced endothelial cell proliferationsCellular Microbiology, 2001
- Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expressionOncogene, 1997
- Parathyroid hormone-related peptide delays terminal differentiation of chondrocytes during endochondral bone developmentEndocrinology, 1996
- The role of antioxidants in gastric carcinogenesisCritical Reviews in Food Science and Nutrition, 1995
- GC box binding induces phosphorylation of Sp1 by a DNA-dependent protein kinaseCell, 1990