# Mechanosensor Function in the Control of Gas Exchange Surface Size and Composition

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $567,884

## Abstract

PROJECT SUMMARY/ABSTRACT
 With each inhalation, exhalation and across development, maturation, aging and
pathogenesis, the lung is constantly under mechanical tension. How the biophysical force is
sensed and responded to remains poorly understood. In the gas exchange region that bears the
front of this force, tension is distributed across the vast alveolar surface. In this study, we will
investigate the central premise that mechanical tension, sensed by alveolar epithelial cells,
triggers a molecular feedback loop that drives the generation and regeneration of the gas
exchange surface area.
 At the center of this feedback loop is Piezo, a large membrane localized channel that is a
quintessential mechanosensor. First discovered and studied in neurons, Piezo genes are also
widely expressed in the lung. Our preliminary data show that while loss of Piezo genes in the
lung mesenchyme or the endothelium did not lead to discernable alveolar structural defects,
inactivating these genes, especially Piezo2, in the lung epithelium led to alveolar simplification
in the early postnatal lung. In the adult lung, Piezo2 loss in the alveolar epithelium led to
drastically increased susceptibility to alveolar damage, leading to fibrosis. In this study, we will
investigate the nature of this mechanosensory circuit in development (Aim 1) and injury repair
(Aim 2). The findings will advance our knowledge on how mechanosensation could tune the size
and composition of the alveolar surface.

## Key facts

- **NIH application ID:** 10720855
- **Project number:** 1R01HL169853-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Xin Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $567,884
- **Award type:** 1
- **Project period:** 2023-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10720855

## Citation

> US National Institutes of Health, RePORTER application 10720855, Mechanosensor Function in the Control of Gas Exchange Surface Size and Composition (1R01HL169853-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10720855. Licensed CC0.

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