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May 20, 2026American Journal of Respiratory and Critical Care Medicine

A74-36 Dissecting Early Fibro-inflammatory Pathways in Human Lung Tissue Ex Vivo

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Authors

LWL WillmerSBS A BrinchIJI Johnsen

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Overview

Randomized trial identifies molecular triggers of fibrosis in human lung tissue, suggesting new treatment avenues.

Key Points

  • The study aims to identify molecular triggers and cytokine combinations that initiate early fibrotic processes in human lung tissue.
  • Precision-cut lung slices from non-fibrotic human lungs were cultured and stimulated with an IPF-relevant cytokine cocktail.
  • The effects of transforming growth factor beta (TGF-β1) and antifibrotic treatments (nintedanib and pirfenidone) were assessed.
  • RNA was analyzed using RT-qPCR, and cytokine levels were measured in culture supernatants.
  • The complete IPF-RC induced pro-fibrotic gene expression, including COL1A1 and ACTA2, with significant alterations in cytokine profiles.
  • Antifibrotic treatment with nintedanib and pirfenidone reduced collagen and ACTA2 levels but did not affect SNAI2 and ZEB2.
  • TGF-β1 predominantly drove collagen synthesis, while IPF-RC without TGF-β1 triggered inflammatory factors and angiogenic markers.

Cite This Study

Willmer et al. (2026) studied this question.

synapsesocial.com/papers/6a0d50cdf03e14405aa9ce0ahttps://doi.org/10.1093/ajrccm/aamag162.2361
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