Hepatocyte growth factor as a key to modulate anti-ulcer action of prostaglandins in stomach

The Journal of Clinical Investigation
M TakahashiM Omata

Abstract

Although the clinical efficacy of prostaglandins (PGs), especially on gastric mucosal injuries induced by nonsteroidal antiinflammatory drugs, is widely appreciated, their mechanism of action, apart from acid suppression, is quite unclear. In this study, we have established a primary culture system of human gastric fibroblasts and clearly demonstrated that PGs strongly induce the expression of hepatocyte growth factor (HGF) in the fibroblasts, which is mediated by PGE specific receptor, EP2 or EP4. Since HGF facilitates repair and protection of gastric epithelial cells in a paracrine manner, it is assumed that some of the beneficial effects of PGs may be mediated by HGF. To confirm this assumption, we established a simplified in vitro culture gastric mucosal model which consists of gastric epithelial cells and gastric fibroblasts. Using the model, we performed a round wound restitution assay. PGE1 remarkably accelerated restitution which was completely inhibited by anti-HGF antibody, indicating that the action was mediated by HGF. To confirm these in vitro data, we further demonstrated that HGF mRNA expression is downregulated at the edges of nonsteroidal antiinflammatory drug-induced gastric ulcers where PGs should be depleted...Continue Reading

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Citations

Sep 27, 2005·Digestive Diseases and Sciences·Katya Gudis, Choitsu Sakamoto
Nov 2, 2006·Digestive Diseases and Sciences·Hisashi TakeharaTakeshi Matsuoka
Sep 17, 2002·European Journal of Pharmacology·Peter C KonturekStanislaw J Konturek
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Sep 20, 2006·Molecular and Cellular Biology·Pei-Chin ChuangShaw-Jenq Tsai
Nov 11, 2003·American Journal of Respiratory and Critical Care Medicine·Marc Peters-Golden
Nov 6, 2009·World Journal of Gastroenterology : WJG·Guang-Liang JiangLarry-A Wheeler
Oct 20, 2009·Journal of the Chinese Medical Association : JCMA·Jiing-Chyuan LuoShou-Dong Lee
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Aug 20, 2003·Alimentary Pharmacology & Therapeutics·M TakahashiH Kuwayama

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