# A role for the stomach in protection from colitis

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $521,231

## Abstract

Project Summary
We have discovered a new function for the stomach in protection from colitis.
Specifically, we have found that a protein called gastrokine-1 (Gkn1), made exclusively
and abundantly in the stomach, is required for protection against inflammatory bowel
disease (IBD). Building on our previous finding that Gkn1 is required for protection from
DSS-induced colitis, we have found that Gkn1 is required for protection against T cell
mediated colitis. Specifically, Gkn1-/- mice develop more severe colitis in the TNBS
(trinitrobenzenesulfonic acid) acute T cell mediated model of IBD. In addition, our
preliminary data suggest that Gkn1-/- x RAG1-/- mice develop more severe colitis in the T
cell transfer model of model of IBD. Thus Gkn1, a stomach specific protein, protects
against colitis.
Gkn1 is a small stable protein containing a secretion signal and a BRICHOS (Bri2,
chondromodulin, and lung surfactant protein C) domain. The secretion signal results in
packaging of Gkn1 into mucus granules of gastric foveolar epithelial cells and release of
Gkn1 into the gastric lumen. The BRICHOS domain is found in a limited number of
mammalian proteins, all of which studied thus far, including Gkn1, are anti-
amyloidogenic. Microbes across all phyla make secreted amyloid containing proteins to
facilitate biofilm formation. Given that Gkn1 is a lumenal protein with anti-amyloidogenic
activity we tested whether Gkn1 inhibits microbial amyloid formation. Our preliminary
data indicates that Gkn1 inhibits microbial amyloid fiber formation and biofilm formation.
We hypothesize that the BRICHOS domain of Gkn1 inhibits amyloid based microbial
biofilms and protects from colitis. We will test this hypothesis with the following aims: (1)
Determine the requirement for Gkn1 in protection from chronic T cell mediated colitis; (2)
Characterize the molecular mechanism of action of Gkn1; (3) Determine the functional
role of Gkn1 activity in protection from colitis.
Together these studies will be significant as they will define a new requirement for Gkn1,
a protein made in the stomach, in protection from colitis. Further these studies will
characterize the molecular mechanism of action of Gkn1 and implicate control of
intestinal amyloids in protection from colitis. Lastly, our work examining preventative
and therapeutic feeding of Gkn1 for protection of colitis may open new therapeutic
opportunities for treatment of IBD.

## Key facts

- **NIH application ID:** 9945503
- **Project number:** 1R01DK124304-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** DAVID L. BOONE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $521,231
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9945503

## Citation

> US National Institutes of Health, RePORTER application 9945503, A role for the stomach in protection from colitis (1R01DK124304-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9945503. Licensed CC0.

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