# Intestinal Mucosal Protection by epidermal Growth Factor

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $342,000

## Abstract

Epithelial tight junction (TJ) is the primary component of intestinal mucosal barrier function
that prevents diffusion of toxins, allergens and pathogens from the gut lumen into mucosa and
eventually to systemic circulation. Disruption of TJs and permeability to injurious factors is
associated with many gastrointestinal (GI) diseases, including radiation-induced GI syndrome
(RIGS). Therefore, understanding the structure and regulation of TJs is essential to our
understanding of the pathogenesis of many GI diseases and design of therapeutic strategies in
treatment of the diseases. Occludin is one of the transmembrane proteins of TJs, the expression and
distribution of which is altered in many GI diseases. The precise function of occludin is unclear. Out
studies so far have identified a phosphorylation hotspot in the C-terminal domain of occludin, which
we named as “Occludin Regulatory Motif (ORM)”. Our preliminary studies show that ORM may be
required for regulation of TJ integrity by interacting with specific proteins, such as MAP7, especially
during radiation-induced injury. Our preliminary data also show that probiotic, Lactobacillus casei (L.
casei) attenuates radiation-induced barrier dysfunction by a mechanism involving epidermal growth
factor receptor (EGFR) tyrosine kinase activity.
 On the basis of above information it is hypothesized that: a) “Occludin Regulatory Motif
(ORM)” plays a role in regulation of tight junction dynamics in the intestinal epithelium, b) occludin-
MAP7 interaction, mediated by oxidative stress and JNK2-cSrc signaling, plays a role in radiation-
induced TJ disruption in the intestinal epithelium and c) oligopeptide factor produced by Lactobacillus
plantarum attenuates radiation-induced tight junction disruption by an EGF receptor-dependent
mechanism. Using both mouse models and Caco-2 cell monolayers we will determine that: 1) ORM
is required for regulation of occludin mobility and tight junction dynamics, 2) Regulatory proteins
interact with ORM by a phosphorylation-dependent mechanism, 3) ORM-MAP7 interaction regulates
TJ dynamics by a phosphorylation-dependent mechanism, 4) ORM-MAP7 interaction is involved in
radiation-induced TJ disruption and barrier dysfunction, 5) Oxidative stress and JNK2-cSrc signaling
mediate radiation-induced alteration of ORM-MAP7 interaction and TJ disruption, 6) L. plantarum
soluble factor attenuates radiation-induced tight junction disruption by suppressing oxidative stress,
JNK2-cSrc signaling and occludin-MAP7 interaction, 7) EGF receptor transactivation is involved in L.
plantarum-mediated TJ protection from radiation, and 8) Oligopeptide factor in L. plantarum is
responsible for epithelial protection from radiation injury. Out come of these studies will open a new
mechanism in epithelial tight junction regulation and therapeutic strategies for treatment of RIGS.

## Key facts

- **NIH application ID:** 9830048
- **Project number:** 5R01DK055532-20
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** RADHAKRISHNA RAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,000
- **Award type:** 5
- **Project period:** 1998-09-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830048

## Citation

> US National Institutes of Health, RePORTER application 9830048, Intestinal Mucosal Protection by epidermal Growth Factor (5R01DK055532-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9830048. Licensed CC0.

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