Basal Stem Cell Signaling Pathways Regulating Collective Epithelial Cell Migration and Airway Repair
- 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA, USA
- 2These authors contribute equally
- 3Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Abstract
The airway epithelium serves as a critical barrier against pathogens, allergens, and other environmental insults. Disruption of this barrier contributes to respiratory diseases such as chronic obstructive pulmonary disease, making rapid epithelial repair essential for maintaining lung function. Basal cells (BCs), the primary regenerative cell population of the proximal airway epithelium, drive repair through coordinated collective cell migration rather than isolated cellular behaviors. This process is closely linked to dynamic transitions between jammed and unjammed tissue states that regulate migratory capacity and tissue remodeling. Emerging evidence identifies extracellular matrix (ECM) remodeling, Wnt, and transforming growth factor-β (TGF-β) signaling as key regulators of these multicellular responses. ECM remodeling establishes the mechanical substrate for migration, while non-canonical Wnt signaling promotes cytoskeletal reorganization, cell polarity, and coordinated BC movement. TGF-β signaling acts as a context-dependent regulator of BC migration, differentiation, epithelial jamming, and cytoskeletal remodeling through canonical and non-canonical pathways. ECM-integrin signaling links the extracellular environment to cytoskeletal dynamics and collective migration, while inflammatory and mechanical cues modify these responses. Integrin αvβ5/αvβ6-mediated interactions with the ECM connect mechanical forces to focal adhesion signaling and activation of latent TGF-β, linking tissue mechanics to epithelial repair. Together, integration of inflammatory, biochemical, and biomechanical signals that coordinate collective migration and epithelial restoration. This mini-review highlights recent advances supporting a model where coordinated ECM remodeling, Wnt signaling, and TGF-β signaling regulate BC migration and restore epithelial barrier integrity following injury, and examines how disruption of these processes contributes to abnormal repair in chronic lung disease.
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BibTeX
@article{nagarajan2026basal,
title = {{Basal Stem Cell Signaling Pathways Regulating Collective Epithelial Cell Migration and Airway Repair}},
author = {Sahana Nagarajan and Emily C. Liu and Amy L. Ryan},
journal = {American journal of physiology. Lung cellular and molecular physiology},
year = {2026},
month = oct,
doi = {10.1152/ajplung.90005.2026},
url = {https://doi.org/10.1152/ajplung.90005.2026},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Basal Stem Cell Signaling Pathways Regulating Collective Epithelial Cell Migration and Airway Repair
AU - Sahana Nagarajan
AU - Emily C. Liu
AU - Amy L. Ryan
PY - 2026
DA - 2026/10/06
JO - American journal of physiology. Lung cellular and molecular physiology
DO - 10.1152/ajplung.90005.2026
UR - https://doi.org/10.1152/ajplung.90005.2026
AB - The airway epithelium serves as a critical barrier against pathogens, allergens, and other environmental insults. Disruption of this barrier contributes to respiratory diseases such as chronic obstructive pulmonary disease, making rapid epithelial repair essential for maintaining lung function. Basal cells (BCs), the primary regenerative cell population of the proximal airway epithelium, drive repair through coordinated collective cell migration rather than isolated cellular behaviors. This process is closely linked to dynamic transitions between jammed and unjammed tissue states that regulate migratory capacity and tissue remodeling. Emerging evidence identifies extracellular matrix (ECM) remodeling, Wnt, and transforming growth factor-β (TGF-β) signaling as key regulators of these multicellular responses. ECM remodeling establishes the mechanical substrate for migration, while non-canonical Wnt signaling promotes cytoskeletal reorganization, cell polarity, and coordinated BC movement. TGF-β signaling acts as a context-dependent regulator of BC migration, differentiation, epithelial jamming, and cytoskeletal remodeling through canonical and non-canonical pathways. ECM-integrin signaling links the extracellular environment to cytoskeletal dynamics and collective migration, while inflammatory and mechanical cues modify these responses. Integrin αvβ5/αvβ6-mediated interactions with the ECM connect mechanical forces to focal adhesion signaling and activation of latent TGF-β, linking tissue mechanics to epithelial repair. Together, integration of inflammatory, biochemical, and biomechanical signals that coordinate collective migration and epithelial restoration. This mini-review highlights recent advances supporting a model where coordinated ECM remodeling, Wnt signaling, and TGF-β signaling regulate BC migration and restore epithelial barrier integrity following injury, and examines how disruption of these processes contributes to abnormal repair in chronic lung disease.
SN - 1040-0605
SN - 1522-1504
ER -