# The role of SPRY2 in the colonic epithelial response to inflammation

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2021 · $380,546

## Abstract

PROJECT SUMMARY/ABSTRACT
These studies are designed to test the novel idea that Sprouty-2 (SPRY2), an intracellular regulator of receptor
tyrosine kinase-induced signaling, is a central gatekeeper restricting colonic epithelial repair responses
including protective changes in secretory differentiation and wound healing. Our preliminary data show that
SPRY2 is downregulated by inflammation in the colonic epithelium. This appears to be a protective or
compensatory response, as mice with intestinal epithelium-specific SPRY2 deletion are resistant to dextran
sulfate sodium (DSS)-induced colitis. Furthermore, these mice display altered intracellular signaling, elevated
interleukin IL-33 levels, more tuft cells, and increased mucus production. Thus, a regulated loss of SPRY2 may
be an important, potentially exploitable, mechanism contributing to repair of the colonic epithelial barrier
following an insult. In this project, we will test the hypothesis that colitis-induced loss of SPRY2 releases
normal homeostatic inhibition of intracellular signaling to promote protective epithelial and epithelial-
mesenchymal responses. Aims of the study are (1) define the influence of SPRY2 on colonic secretory cell
differentiation and function; (2) test the role of SPRY2 in epithelial wound repair, and (3) determine whether
SPRY2 downregulation drives recovery from colitis. We will test the central hypothesis with coordinated in vitro
and in vivo models including human and mouse primary colonic epithelial culture, cell culture models, and in
vivo colitis using conditional knockout mice or mice in which SPRY2 levels are manipulated through
nanoparticle-delivered expression constructs.

## Key facts

- **NIH application ID:** 10164769
- **Project number:** 5R01DK119694-03
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Mark R Frey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $380,546
- **Award type:** 5
- **Project period:** 2019-08-20 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164769

## Citation

> US National Institutes of Health, RePORTER application 10164769, The role of SPRY2 in the colonic epithelial response to inflammation (5R01DK119694-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10164769. Licensed CC0.

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