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Tristetraprolin prevents gastric metaplasia by suppressing pathogenic inflammation

ABSTRACT: Purpose: The goals of this study are to examine whether TTP can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM). Methods: we utilized the TTP∆ARE mouse model to examine whether TTP overexpression can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM). Results: We found that TTP∆ARE mice were completely protected from ADX-induce gastric inflammation and SPEM. RNA sequencing revealed that TTP overexpression suppressed the expression of genes associated with the innate immune response. Finally, we show that protection from gastric inflammation was only partially due to suppression of Tnf, a well-known TTP target. Conclusions: Our results demonstrate that TTP exerts broad anti-inflammatory effects in the stomach, and suggest that therapies that increase TTP expression may be effective treatments of pro-neoplastic gastric inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE164349 | GEO | 2021/11/10

REPOSITORIES: GEO

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Endogenous glucocorticoids suppress spontaneous gastric inflammation and spasmolytic polypeptide expressing metaplasia

Project description:Adrenalectomy induced severe eosinophil and macrophage infiltration localized to the gastric corpus resulting in development of spasmolytic polypeptide expressing metaplasia (SPEM) and oxyntic atrophy. RNA sequencing analysis revealed significant upregulation of proinflammatory genes 3 days post-adrenalectomy, prior to leukocyte infiltration and histopathological changes.

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