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Targeting the Epigenetic Regulator CBX5 Promotes Fibroblast Metabolic Reprogramming and Inhibits Lung Fibrosis.

Jeongmin Hong1,2, Tho X Pham1, Jisu Lee1

  • 1Department of Medicine.

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|December 6, 2024
PubMed
Summary
This summary is machine-generated.

Chromobox protein homolog 5 (CBX5) epigenetically regulates lung fibroblast metabolism, inhibiting collagen production and fibrosis. Targeting CBX5 may offer new treatments for idiopathic pulmonary fibrosis (IPF).

Keywords:
bleomycinepigeneticsfibroblastsmetabolic reprogrammingpulmonary fibrosis

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Area of Science:

  • Cell Biology
  • Epigenetics
  • Pulmonary Medicine

Background:

  • Idiopathic pulmonary fibrosis (IPF) involves persistent fibroblast activation and excessive collagen deposition.
  • Epigenetic and metabolic changes are implicated in fibroblast activation but their interplay is unclear.

Purpose of the Study:

  • To investigate the role of the epigenetic regulator CBX5 in fibroblast activation and metabolic reprogramming in IPF.
  • To explore CBX5 as a potential therapeutic target for IPF.

Main Methods:

  • Studied CBX5 function in bleomycin-induced lung injury models and IPF patient samples.
  • Utilized single-cell and bulk RNA sequencing, immunohistochemistry, and metabolic assessments.
  • Investigated CBX5 inhibition effects with metformin on IPF fibroblasts and lung explants.

Main Results:

  • Loss of CBX5 attenuated lung fibrosis and downregulated profibrotic genes while upregulating antifibrotic metabolic genes.
  • CBX5 is enriched in pathogenic fibroblasts in IPF lungs.
  • CBX5 silencing inhibited glycolysis, enhanced AMPK signaling, and improved mitochondrial metabolism in IPF fibroblasts.
  • CBX5 pathway interruption potentiated metformin's effects, inhibiting collagen secretion.

Conclusions:

  • CBX5 is a critical epigenetic regulator linking fibroblast metabolic dysfunction to persistent activation in IPF.
  • Targeting CBX5 offers a promising strategy to ameliorate fibrosis by modulating fibroblast metabolism.