# The role of ErbB3-induced Pmp22 in intestinal barrier function

> **NIH NIH F31** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2021 · $46,036

## Abstract

PROJECT SUMMARY/ABSTRACT
The intestinal epithelium is critical in the maintenance of gut health and function. It absorbs nutrients and
water, while also acting as a barrier to separate luminal contents and the microbiota from the rest of the body.
Intestinal stem cells (ISCs) are central to the formation and regeneration of this barrier. Barrier dysfunction is
associated with diseases such as inflammatory bowel disease, celiac disease, and irritable bowel syndrome.
Despite the importance it has in intestinal disorders, there are currently no treatments that target the barrier.
My preliminary data suggest that the ErbB3 receptor tyrosine kinase is important in maintenance of this barrier,
as mice with ErbB3 deletion in the intestinal epithelium (ErbB3-IEKO) have increased intestinal permeability.
Previous studies implicated ErbB3 and its ligand Nrg-1β as important factors in epithelial barriers, as Nrg-1β
promotes tight junction formation in airway epithelial cells; however, ErbB3’s role in maintenance of the
intestinal barrier is as yet poorly understood. We find that ErbB3-IEKO mice have markedly reduced
expression of Pmp22, a component of epithelial tight junctions originally described as in the myelin sheath of
peripheral nerves. In this project, I will test the hypothesis that ErbB3 promotes tight junction formation and
maintenance in the intestinal epithelium through induction of Pmp22. In the first aim, I will define the role of
Pmp22 in regulating tight junctions in the intestinal epithelium. This will be done through intestinal epithelial cell
lines with Pmp22 knocked down or overexpressed via transfection, and mice given intraperitoneal injection of
Nrg-1β to induce Pmp22 expression. In the second aim, I will determine how Pmp22 is regulated in the
epithelium through the use of the small molecules inhibiting pathways downstream of ErbB3 in intestinal
epithelial cells. Because ErbB3 requires a heterodimerization partner for signaling, I will also determine which
ErbB family members are required for EbB3-driven Pmp22 expression. The proposed research will advance
knowledge of how the intestinal barrier is formed and regulated, and ultimately will work towards developing
barrier maintenance as a therapeutic target for inflammatory diseases in the gut.

## Key facts

- **NIH application ID:** 10388418
- **Project number:** 1F31DK131856-01
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Jonathan Jay Hsieh
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388418

## Citation

> US National Institutes of Health, RePORTER application 10388418, The role of ErbB3-induced Pmp22 in intestinal barrier function (1F31DK131856-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10388418. Licensed CC0.

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