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Updated: Jul 27, 2025

Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
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Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica

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Mitochondrial folate pathway regulates myofibroblast differentiation and silica-induced pulmonary fibrosis

Yaqian Qu1,2, Ruonan Zhai1,3,4, Dandan Wang3,4

  • 1Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.

Journal of Translational Medicine
|June 6, 2023
PubMed
Abstract

Insights

Mitochondrial folate metabolism proteins regulate fibroblast to myofibroblast differentiation, a key process in silica-induced pulmonary fibrosis (silicosis). Folate supplementation suppressed this process and reduced fibrosis in mice.

Area of Science:

  • Cell Biology
  • Pulmonary Medicine
  • Biochemistry

Background:

  • Silica-induced pulmonary fibrosis (silicosis) involves excessive extracellular matrix deposition in lung tissue.
  • Fibroblast to myofibroblast differentiation is a critical driver of silicosis progression.
  • Targeting myofibroblast differentiation presents a potential therapeutic strategy for pulmonary fibrosis.

Purpose of the Study:

  • To investigate the role of mitochondrial folate metabolism in myofibroblast differentiation.
  • To explore the potential of targeting mitochondrial folate pathway for silicosis treatment.

Main Methods:

  • Myofibroblast differentiation induced in human lung fibroblasts using TGF-β in vitro.
  • Pulmonary fibrosis induced in mice using silica exposure in vivo.
  • Quantitative mass spectrometry used to identify differentially expressed proteins.

Main Results:

  • Proteins in the mitochondrial folate pathway, including MTHFD2 and SLC25A32, were upregulated during myofibroblast differentiation.
  • These proteins were found to negatively regulate myofibroblast differentiation.
  • Reduced plasma folate levels observed in silicosis patients and mice.
  • Folate supplementation increased MTHFD2 and SLC25A32 expression, reduced oxidative stress, and suppressed myofibroblast differentiation and silicosis in mice.

Conclusions:

  • The mitochondrial folate pathway plays a regulatory role in myofibroblast differentiation.
  • This pathway represents a potential therapeutic target for mitigating silica-induced pulmonary fibrosis.
Keywords:
FolateMTHFD2MitochondriaOxidative stressSLC25A32Silicosis

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