{
  "abstract": "Background The cholecystokinin-2/gastrin receptor (Cck2r) is expressed in corpus isthmus progenitor, enterochromaffin-like and parietal cells, regulating acid secretion and cell turnover. However, the role of gastrin on Cck2r progenitors during mucosal regeneration remains unexplored.Objective To study the role of gastrin-Cck2r axis and corpus progenitors during gastric injury and regeneration.Design We generated Cck2r-CreERT2; Gastrin-DTR-p2A-TdTomato; Rosa26-ZsGreen mice to trace corpus Cck2r + progenitors during homeostasis and injury, under conditions of hypogastrinaemia and hypergastrinaemia. Injury models included acute ulceration, chronic H. pylori gastritis and N-Nitroso-N-Methylurea (MNU) exposure.Results Hypergastrinaemia significantly expanded Cck2r + isthmus progenitors, whereas hypogastrinaemia reduced them. Gastric ulceration induced a twofold elevation in plasma gastrin by day 14, antral G-cell expansion and complete ulcer healing by day 28. Gastrin infusion or proton pump inhibitor (PPI) treatment further elevated gastrin and promoted complete ulcer healing by day 14, whereas G-cell ablation minimised gastrin, impaired healing and abrogated the benefits of PPI (p<0.05). The vagus nerve, through the muscarinic receptor 3, mediated both gastrin elevations and Cck2r+ progenitor expansion during ulcer healing. G-cell ablation in H. pylori-infected mice increased colonisation and exacerbated inflammation, atrophy, metaplasia and dysplasia (p<0.05), while hypergastrinaemia was protective. Similarly, in the MNU model, G-cell ablation worsened gastric pathology while hypergastrinaemia mitigated it.Conclusions We report a novel role for G-cell-derived gastrin in ulcer healing. Hypogastrinaemia is a risk factor for poor ulcer healing, corpus atrophy and potentially cancer, while physiological gastrin responses are protective. PPI-induced hypergastrinaemia plays a key role in ulcer healing, and gastrin signalling may prevent gastric preneoplasia.",
  "authors": [
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA",
        "Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China",
        "Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Disease, Fuzhou, Fujian, China"
      ],
      "name": "Biyun Zheng"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Hiroki Kobayashi"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA",
        "Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"
      ],
      "name": "Ruhong Tu"
    },
    {
      "affiliations": [
        "Department of Biological Sciences, Columbia University, New York, New York, USA"
      ],
      "name": "Kexuan Huang"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA",
        "Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China"
      ],
      "name": "Xiaofei Zhi"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA",
        "Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"
      ],
      "name": "Guodong Lian"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Feijing Wu"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Jin Qian"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Yosuke Ochiai"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Quin T Waterbury"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Ermanno Malagola"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China",
        "Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Disease, Fuzhou, Fujian, China"
      ],
      "name": "Jiaoqian Lu"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Masahiro Hata"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Yi Zeng"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA",
        "Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"
      ],
      "name": "Hualong Zheng"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Puran Zhang"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Shuang Li"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"
      ],
      "name": "Leah Zamechek"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China",
        "Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Disease, Fuzhou, Fujian, China"
      ],
      "name": "Xiaozhong Wang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China",
        "Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Disease, Fuzhou, Fujian, China"
      ],
      "name": "Fenglin Chen"
    },
    {
      "affiliations": [
        "Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA",
        "Columbia University Digestive and Liver Disease Research Center, Columbia University, New York, New York, USA"
      ],
      "name": "Timothy C Wang"
    }
  ],
  "title": "Gastrin-dependent expansion of Cck2r+ corpus progenitors accelerates ulcer healing and inhibits gastric dysplasia",
  "uid": "a2626be2-837a-5f78-8137-d5b79f49d74a"
}