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Transforming growth factor-β1 downregulates tryptophanyl-tRNA synthetase expression in human lung fibroblasts

Aaron K McDowell-Sanchez1, Konstantin Tsoyi2

  • 1Department of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, United States.

Advances in Medical Sciences
|February 18, 2026
PubMed
Abstract

Insights

Transforming growth factor-beta 1 (TGF-β1) downregulates tryptophanyl-tRNA synthetase (WARS) expression in lung fibroblasts via the YY1 transcription factor. WARS treatment minimally impacts profibrotic responses in activated human lung fibroblasts.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Fibrosis Research

Background:

  • The function of tryptophanyl-tRNA synthetase (WARS) in lung fibroblasts remains uncharacterized.
  • Transforming growth factor-beta 1 (TGF-β1) is a key mediator of fibrosis.

Purpose of the Study:

  • To investigate the effect of TGF-β1 on WARS expression in human lung fibroblasts.
  • To determine if WARS regulates profibrotic responses.

Main Methods:

  • Utilized human lung fibroblast cell lines (MRC-5) and primary cells (HLFs).
  • Assessed WARS expression using ELISA and Western blot.
  • Measured profibrotic markers (fibronectin, collagen1, αSMA) via Western blot, gel contraction, and RT-qPCR.

Main Results:

  • TGF-β1 significantly downregulated WARS expression in lung fibroblasts.
  • Yin Yang 1 (YY1) transcription factor silencing partially reversed TGF-β1's inhibitory effect on WARS.
  • Recombinant WARS inhibited fibronectin but not collagen1 or αSMA in TGF-β1-activated fibroblasts.

Conclusions:

  • TGF-β1 inhibits WARS expression through YY1 in lung fibroblasts.
  • WARS has a limited role in modulating TGF-β1-induced profibrotic responses in these cells.
Keywords:
Lung fibroblastsPulmonary fibrosisTransforming growth factor-betaWARS1

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