CD44 variant isoform 9 emerges in response to injury and contributes to the regeneration of the gastric epithelium

The Journal of Pathology
Nina Bertaux-SkeirikYana Zavros

Abstract

The CD44 gene encodes several protein isoforms due to alternative splicing and post translational modifications. Given that CD44 variant isoform 9 (CD44v9) is expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands during repair, CD44v9 may be play a funcitonal role during the process of regeneration of the gastric epithelium. Here we hypothesize that CD44v9 marks a regenerative cell lineage responsive to infiltrating macrophages during regeneration of the gastric epithelium. Ulcers were induced in CD44-deficient (CD44KO) and C57BL/6 (BL6) mice by a localized application of acetic acid to the serosal surface of the stomach. Gastric organoids expressing CD44v9 were derived from mouse stomachs and transplanted at the ulcer site of CD44KO mice. Ulcers, CD44v9 expression, proliferation and histology were measured 1, 3, 5 and 7-days post-injury. Human-derived gastric organoids were generated from stomach tissue collected from elderly (>55 years) or young (14-20 years) patients. Organoids were transplanted into the stomachs of NOD scid gamma (NSG) mice at the site of injury. Gastric injury was induced in NRG-SGM3 (NRGS) mice harboring human-derived immune cells (hnNRGS) and the immune profile anlayzed by CyT...Continue Reading

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Citations

Feb 22, 2018·Nature Reviews. Gastroenterology & Hepatology·José B Sáenz, Jason C Mills
Jan 18, 2019·The Journal of Clinical Investigation·Jonathan T BusadaJohn A Cidlowski
May 21, 2020·The Journal of Pathology·Katherine M RieraJames R Goldenring
Aug 7, 2020·American Journal of Physiology. Cell Physiology·Emma TealYana Zavros
Sep 2, 2019·Cellular and Molecular Gastroenterology and Hepatology·Takahiro ShimizuJames R Goldenring
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Sep 4, 2020·Cellular and Molecular Gastroenterology and Hepatology·Megan T HoffmanHoward C Crawford
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Aug 30, 2021·Cellular and Molecular Gastroenterology and Hepatology·Su-Hyung LeeJames R Goldenring
Aug 7, 2021·Cellular and Molecular Gastroenterology and Hepatology·Jonathan T BusadaPerry J Blackshear
Sep 30, 2021·Cellular and Molecular Gastroenterology and Hepatology·Christine N NotoRichard J DiPaolo
Nov 4, 2021·Gastroenterology·James R Goldenring, Jason C Mills

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