# Mechanotransduction in gastrointestinal physiology

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $652,227

## Abstract

PROJECT SUMMARY/ABSTRACT
Disruptions in mechanosensation are commonly responsible for symptoms in diseases of gut-brain interaction
(DGBI), like irritable bowel syndrome (IBS), which affect ~15% of the US population. Therefore, my laboratory’s
long-term goal is to elucidate the cellular and molecular mechanisms of gastrointestinal (GI) mechanosensitivity
in health and in DGBIs.
There are several mechanosensory pathways in the GI tract. One such important mechanosensory pathway that
is involved in DGBIs is initiated through the specialized sensory epithelial enteroendocrine cells (EECs). Upon
stimulation, EECs release diverse signaling molecules that have a range of physiologic effects, and disruption
in this signaling is involved in DGBIs. We discovered an EECs sub-population which is mechanosensitive. These
EECs express Piezo2, a mechano-gated ion channel that connects forces to release of EEC signaling molecules
and endows the intestine with an ability to sense small luminal forces to adjust GI motility and secretion.
The objective of this proposal, based on strong rationale and extensive preliminary data, is to test the hypothesis
that rectal Piezo2+ mechanosensitive EECs co-express select GPCRs sensitive to digestive metabolites, which
modulate Piezo2 mechanosensitivity. These rectal mechanosensitive EECs connect chemo- and mechano-
signaling in rectal EECs, and thereby regulate regional and proximal intestinal motility. We have established
novel transgenic mouse models that allow us to lineage track, stimulate, and interrogate specific EEC sub-
populations, and we will use these mouse models and validated EEC lines with a range of innovative and
established gold-standard approaches from single cells to in vivo to study mechanosensitive EECs and their
roles in GI physiology. Aim 1 will determine the cellular mechanisms of chemo- and mechano-signaling in EECs.
Aim 2 will determine how the mechanosensitive EECs stimulated by forces and luminal digestive metabolite to
modulate GI motility.
The proposed experiments are foundationally linked to our previous work, but they represent a new and exciting
direction and can be completed in the defined award period. The results from this study are important because
they will allow us to deeply understand mechanosensitive EEC cellular physiology and their roles in GI motility,
which will enable us to examine alterations in disease, and then potentially target these pharmacologically as
novel and specific therapies for DGBIs.

## Key facts

- **NIH application ID:** 10905782
- **Project number:** 2R01DK123549-06
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Arthur Beyder
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $652,227
- **Award type:** 2
- **Project period:** 2019-09-17 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10905782

## Citation

> US National Institutes of Health, RePORTER application 10905782, Mechanotransduction in gastrointestinal physiology (2R01DK123549-06). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10905782. Licensed CC0.

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