# Laminin Binding Integrins in Lung Development

> **NIH NIH R03** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $86,500

## Abstract

PROJECT SUMMARY
The overall goal of our research program is to define how cell-extracellular matrix (ECM) interactions regulate
lung development and alveolar homeostasis in health and disease. Epithelial cells connect with the
surrounding ECM through integrins, transmembrane protein receptors comprised of an a and b subunit.
Integrins are required for signaling between epithelial cells and the ECM and regulate critical cell processes,
such as adhesion, migration, proliferation, differentiation and cell survival. Laminin is one of the major
components of the lung basement membrane, a specialized ECM structure. Laminin binding integrins are
required for organogenesis in other branched organs such as the kidney, mammary gland, and submandibular
gland, but are relatively understudied in the lung. Integrins are expressed in a temporally and spatially specific
manner that influences their ECM ligand binding avidity. The precise laminin-integrin interactions that regulate
fetal lung development are currently unknown. From our preliminary work, we have identified a3b1 and a6b1
as the critical integrins in lung development. Our murine deletion of a6 integrin in the lung epithelium
demonstrates a critical role in early lung branching morphogenesis. New airways branch at pressure points,
where epithelial cells must stop and pivot to advance airway growth in a new direction. In their role as
mechanoreceptors, integrins are perfectly poised to direct the speed and direction of epithelial growth.
Integrins also signal changes in the alveolar microenvironment and influence epithelial behavior. Deletion of a3
in the murine lung results in sacculation, alveolarization, and epithelial differentiation defects. Epithelial
differentiation is required for proper alveolarization and the epithelial response to injury. We have previously
shown that epithelial b1 integrin, binding partner to a3 integrin, is required for the normal epithelial response
after injury. Thus, in this proposal, we will test the hypothesis that a6b1 integrin is the dominant laminin
receptor for regulation of branching morphogenesis, whereas a3b1 is required for alveolarization.
AIM 1: Determine the specific roles for laminin binding integrins in branching morphogenesis.
AIM 2: Define the role of laminin binding integrins during sacculation and alveolarization.

## Key facts

- **NIH application ID:** 10064461
- **Project number:** 1R03HL154287-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Erin J Plosa
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $86,500
- **Award type:** 1
- **Project period:** 2020-08-05 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064461

## Citation

> US National Institutes of Health, RePORTER application 10064461, Laminin Binding Integrins in Lung Development (1R03HL154287-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10064461. Licensed CC0.

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