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August 22, 2026Cell Communication and SignalingOpen Access

Differentiation arrest of transitional alveolar epithelial cells drives pulmonary fibrosis

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Authors

HCHaotian ChengRLRuiyan LiuYZYan Zhou

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Overview

Review demonstrates how differentiation arrest of transitional alveolar epithelial cells drives pulmonary fibrosis progression, highlighting targets for epithelial-directed therapies.

Key Points

  • To synthesize evidence on the molecular mechanisms governing differentiation arrest in transitional alveolar epithelial cells and their role in driving pulmonary fibrosis.
  • Literature synthesis of single-cell sequencing and functional studies evaluating alveolar epithelial type 2 (AEC2) to type 1 (AEC1) cell differentiation.
  • Evaluation of aberrant molecular cascades including Wnt, YAP/TAZ, and Notch signaling, metabolic reprogramming, and epigenetic modifications.
  • Arrest of transitional Krt8+ intermediate epithelial cells impairs alveolar barrier restoration and creates active profibrotic signaling hubs.
  • Persistent transitional cells actively remodel the extracellular microenvironment and stimulate stromal compartments to sustain a self-reinforcing fibrotic niche.

Cite This Study

Cheng et al. (2026) studied this question.

synapsesocial.com/papers/6a895f62ca7ade938187e086https://doi.org/10.1186/s12964-026-03163-w
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Reciprocal Paracrine Signaling and Dynamic Coordination of Transitional States in the Alveolar Epithelial Type 2 Cells and Associated Alveolar Lipofibroblasts During Homeostasis, Injury and Repair2025
  2. 2Reciprocal Paracrine Signaling and Dynamic Coordination of Transitional States in the Alveolar Epithelial Type 2 Cells and Associated Alveolar Lipofibroblasts During Homeostasis, Injury and Repair2025
  3. 3Cell competition drives bronchiolization and pulmonary fibrosis.2024
  4. 4A74-18 Alveolar Epithelial Cell Senescence Promotes Fibrosis by Limiting Repair After Injury2026
  5. 5Emergence of Disease-relevant Aberrant Epithelial Cell States in Human Alveolar Organoids2026