Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells

• Published in: Biochemical and biophysical research communications 2010-07, Vol.398 (3), p.581-584
• Main Authors: Shibuya, Akiko, Onda, Kenji, Kawahara, Hirofumi, Uchiyama, Yuka, Nakayama, Hiroko, Omi, Takamasa, Nagaoka, Masayoshi, Matsui, Hirofumi, Hirano, Toshihiko
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; Animals; Anti-Ulcer Agents - pharmacology; Cell Line; Chalcones - pharmacology; CONCENTRATION RATIO; CULTURE MEDIA; Cytoprotection; Gastric Mucosa - blood supply; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gene Knockdown Techniques; GROWTH FACTORS; HEAT-SHOCK PROTEINS; HEME; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Heme-oxygenase-1; INDUCTION; MUCOUS MEMBRANES; Neovascularization, Physiologic - drug effects; NF-E2-Related Factor 2 - metabolism; Rat gastric epithelial cells; RATS; RNA, Small Interfering - genetics; Sofalcone; TRANSLOCATION; ULCERS; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2010.06.124

► Sofalcone increases HO-1 in gastric epithelial cells. ► The induction of HO-1 by sofalcone treatment follows the activation of Nrf2. ► The production of VEGF by sofalcone treatment is mediated by HO-1 induction. Sofalcone, 2′-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of sofalcone on HO-1 induction in gastrointestinal tissues is not clear. In the current study, we investigated the effects of sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited sofalcone-induced VEGF production, suggesting that the effect of sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.