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    Home > Biochemistry News > Biotechnology News > The team from the Second Hospital of Zhejiang University found a potential target for the treatment of gastric mucosal injury

    The team from the Second Hospital of Zhejiang University found a potential target for the treatment of gastric mucosal injury

    • Last Update: 2021-09-11
    • Source: Internet
    • Author: User
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    Researchers at the Second Affiliated Hospital of Zhejiang University School of Medicine have recently discovered a potential therapeutic target for gastric mucosal injury

    Hyperacidity, long-term drinking, Helicobacter pylori infection, and non-steroidal anti-inflammatory drugs can all cause gastric mucosal damage

    Gastric epithelial progenitor cells (EPC), especially Lgr5+ EPC, play a key role in the rapid repair of damaged gastric mucosal epithelium

    In previous studies, the research team discovered a new mitochondrial protein-ankyrin repeat domain protein 22 (ANKRD22)

    Deletion of ANKRD22 promotes rapid proliferation of Lgr5+ EPC

    The researchers established an acute gastric mucosal injury model in Ankrd22 +/+ mice by gavage with acidified ethanol , and commissioned Saiye to establish an Ankrd22 -/- mouse model

    Later, they hope to determine the identity of these proliferating cells

    Given that the Wnt pathway plays a key role in the proliferation of Lgr5+ EPC, the researchers next analyzed whether the inhibitory effect of ANKRD22 on the proliferation of Lgr5+ EPC is mediated through the Wnt pathway

    Deletion of ANKRD22 reduces gastric epithelial inflammation

    In order to study the underlying mechanism of the reduction of inflammation in Ankrd22 -/- mice, the researchers carried out a series of analyses and found that the proportion of white blood cells in the stomach epithelium of Ankrd22 -/- mice was significantly lower than that in Ankrd22 +/+ mice, and TNF-α The concentration of IL-1α and IL-1α were also significantly reduced, indicating that the absence of ANKRD22 reduced gastric epithelial inflammation during gastric mucosal injury

    Since macrophages play an important role in mediating inflammation, how does the expression of ANKRD22 affect the function of macrophages? They stimulated human and mouse macrophages through IFN-γ and LPS, and found that ANKRD22 expression increased significantly after macrophages were activated

    ANKRD22 inhibitor relieves gastric mucosal damage

    Afterwards, the researchers used molecular docking models to screen out compounds that interact with key sites L122/D132, and identified the lead compound AV023 that inhibits ANKRD22

    They then explored the effect of AV023 on Lgr5+ EPC accumulation and inflammation in a mouse model of acute gastric mucosal injury

    Concluding remarks

    The author believes that ANKRD22 may be an ideal therapeutic target to promote the repair of gastric mucosal damage

    Original Search

    Liu J, Wu J, Wang R, Zhong D, Qiu Y, Wang H, Song Z, Zhu Y.

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