Article1 min read·Published Jan 2017Older

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

Part of Intestinal Stem Cells & Regeneration 24 items

pubmed.ncbi.nlm.nih.gov

Michael Helmrath

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 CyTOF. CD44v9 expression emerged within regenerating glands the ulcer margin in response to injury. While ulcers in BL6 mice healed within 7-days post-injury, CD44KO mice exhibited loss of repair and epithelial regeneration. Ulcer healing was promoted in C

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Article · Jan 2017 · 1 min read

In brief

This study demonstrates that CD44 variant isoform 9 (CD44v9) marks a regenerative cell lineage essential for gastric epithelial repair following injury. Using CD44-deficient mice and organoid transplantation models, researchers show that CD44v9 expression emerges at ulcer margins and is required for successful healing, with potential implications for age-related differences in gastric repair capacity.

Written by the GCMD Library team from the article.

Michael Helmrath

Statements in this article

CD44 variant isoform 9 (CD44v9) is expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands during repair.
Research
Gastric ulcers were induced in mice by localized application of acetic acid to the serosal surface of the stomach.
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Ulcers, CD44v9 expression, proliferation and histology were measured at 1, 3, 5 and 7 days post-injury.
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Human-derived gastric organoids were generated from stomach tissue collected from elderly patients over 55 years or young patients aged 14-20 years.
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CD44v9 expression emerged within regenerating glands at the ulcer margin in response to injury.
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Ulcers in C57BL/6 mice healed within 7 days post-injury.
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CD44-deficient mice exhibited loss of repair and epithelial regeneration.
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