Human antigen R promotes lung fibroblast differentiation to myofibroblasts and increases extracellular matrix production

Apr 15, 2021Journal of cellular physiology

Human antigen R helps lung cells become scar-forming cells and boosts tissue buildup

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Abstract

In human lung fibroblasts treated with transforming growth factor β1 (TGF-β1), there was a significant increase in the translocation of HuR from the nucleus to the cytoplasm.

  • HuR is an RNA binding protein that stabilizes messenger RNA, potentially influencing protein levels involved in fibrosis.
  • Knockdown of HuR led to a significant reduction in α-SMA protein and the extracellular matrix proteins COL1A1, COL3A, and FN in TGF-β-treated human lung fibroblasts.
  • HuR was found to bind to mRNA for ACTA2, COL1A1, COL3A1, and FN, indicating its role in regulating these genes.
  • While HuR knockdown affected the mRNA stability of ACTA2, it did not have the same effect on the ECM genes COL1A1, COL3A1, or FN.
  • Mouse models of pulmonary fibrosis showed higher levels of cytoplasmic HuR in lung structural cells compared to controls.
  • In human lungs affected by idiopathic pulmonary fibrosis, increased cytoplasmic HuR was also observed.

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