Improve gastric ulcers!SEMAPHORIN-PLEXIN-Rasal1 signaling pathway regulate gastric acid secretion

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Gastric acid has many important physiological functions, such as digestion food, inhibiting harmful bacteria, and promoting mineral absorption. However, excessive gastric acid may also have potential negative effects, such as damage to mucous membranes, and then participate in the pathological process of gastrointestinal ulcers. Gastrointestinal ulcers usually occur in the initial stage of the stomach and duodenum, and their typical characteristics are the uncertainty of the mucosal barrier. The disease is more difficult and tricky, and may cause complications of life. Therefore, precise regulation of gastric acid secretion is necessary.

近日，Science Translational Medicine在线发表了来自德国马尔堡大学/马克斯-普朗克心肺研究所的Thomas Worzfeld教授团队的最新研究：A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers。 Through organ, biochemical, and in vivo experiments, the effects of Semaphorin-PLEXIN-Rasal1 signaling pathway on gastrin, regulation on gastric acid secretion, and improvement of gastrointestinal ulcers.

G cells are the core link of gastric acid regulation. It releases gastrin (gastrin), and then promotes gastric acid secretion. However, the regulation mechanism of gastrin expression in G cells is currently known. In this study, the author observed Plexin-B1, a transgender receptor protein has a specific expression in G cells of the gastric epithelium. Organoid experiments (Organoid) experiments show that when the Plexin-B1 receptor is activated by its ligand SEMAPHORIN, the expression of gastrin is significantly reduced. Conversely, knockout these Semaphorin ligands in mice will cause the concentration of gastricin in plasma to increase.

Through systematic SIRNA screening, and corresponding biochemical experiments, cell experiments and mouse experiments, research revealed that Rasal1 is the core link of regulating gastric acid secretion of Plexin-B1 signal. The activity of Small GTPase R-Ras to suppress gastric acid secretion. The rats of Rasal1 gene knockout have higher concentrations of plasma and gastrin, and show more serious damage in the digestive tract ulcer model induced by non -steroidal anti -inflammatory drugs (NSAID). Non -steroidal anti -inflammatory drugs (NSAID) are one of the main causes of gastrointestinal ulcers of human beings.

In order to verify whether the Plexin-B1-Rasal1 signaling pathway can be used as a potential treatment target, the author injected one of the Plexin-B1 ligands-SEMAPHORIN 4D restructuring protein for the gastrointestinal ulcer model mice. The results showed that among mice, the Semaphorin 4D can reduce the plasma concentration of gastrin, thereby reducing gastric acid secretion; and significantly improved the gastrointestinal — duodenal ulcers induced by non -steroidal anti -inflammatory drugs.

In summary, this study reveals a regulation mechanism of G cells, which provides a new possibility for the treatment of gastrointestinal ulcerative diseases at the pharmacological level.

Dr. Xu Rui, who graduated from the Institute of Matthew and Lung, Germany, is the first author of the study. The author of the communications is Professor Thomas Worzfeld, director of the Institute of Pharmaceutical Research Institute of the University of Medicine, and he is also a guest professor at the Department of Pharmacology at the Institute of Pharmacology and CPCC, and cooperates closely with the Malp Institute. Professor Thomas Worzfeld's team is rich in scientific research resources and pays attention to talent training. Welcome to join the PhDs who love scientific research. Project group web link:

https://www.uni-marburg.de/en/FB20/Departments/bpc/PharMatoxikol

Original link:

http://doi.org/10.1126/scitranslmed.abf1922

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