Logo image
Back
Basal Stem Cell Signaling Pathways Regulating Collective Epithelial Cell Migration and Airway Repair
Journal article   Open access   Peer reviewed

Basal Stem Cell Signaling Pathways Regulating Collective Epithelial Cell Migration and Airway Repair

Sahana Nagarajan, Emily C Liu and Amy L Ryan
American journal of physiology. Lung cellular and molecular physiology
10/06/2026
DOI: 10.1152/ajplung.90005.2026
PMID: 42838539
url
https://doi.org/10.1152/ajplung.90005.2026View
Published (Version of record) Open Access

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.
 Wnt-Signaling Basal stem cells Epithelium TGF-beta Signaling Airway Collective cell migration

Details

Metrics

1 Record Views
Logo image