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Early growth response‐1 in the pathogenesis of cysteamineinduced duodenal ulcer
Author(s) -
Khomenko Tetyana,
Deng Xiaoming,
Patel Khushin N,
Sandor Zsuzsanna,
Szabo Sandor
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.645.10
Subject(s) - pathogenesis , gene expression , platelet derived growth factor receptor , endocrinology , medicine , vascular endothelial growth factor , microrna , growth factor , basic fibroblast growth factor , biology , messenger rna , gene , microbiology and biotechnology , chemistry , vegf receptors , biochemistry , receptor
We showed earlier that the immediate‐early gene & its zinc finger transcription factor early growth response (Egr) product were enhanced, including the expression of target genes (e.g., bFGF, PDGF, VEGF) in early stage of cysteamine (C)‐induced DU. Our recent studies demonstrated that deletion of egr‐1 gene led to 4.4‐fold increase in C‐induced DU in egr‐1 knockout (KO) vs. wild‐type (WT) mice. mRNA expression of bFGF, VEGF & PDGF was still increased but protein expression of bFGF, VEGF & PDGF was diminished in egr‐1 KO mice. We hypothesized that specific miRNAs in egr‐1 KO mice might be activated & inhibit protein synthesis of egr‐1 target genes. Using miRXplore Microarray study we found that 11 miRNAs (e.g., mir‐696, mir‐467E, mir‐152 & mir‐301B) were elevated by 1.8‐ to 1.9‐fold in egr‐1 KO mice vs. WT mice. Mir‐1892 decreased by 1.7‐fold in egr‐1 KO vs. WT mice. These miRNAs partially share validated targets relating to growth factor responses, e.g., FGFR3 & VEGF. We also demonstrated that DU was significantly reduced in rats treated with adenovirus encoding egr‐1 on days 7 & 14 (p < 0.05) respectively. The mRNA & protein expressions of egr‐1, bFGF, VEGF & PDGF markedly increased in rats after egr‐1 gene therapy. We conclude that Egr‐1 plays a preventive role in the pathogenesis of DU & further studies are needed to identify miRNA expression in egr‐1 KO & WT mice with DU. (This work was supported by the Veterans Health Administration Merit Review Grant to S. Szabo).