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The mechanism of NRF2 regulating cell proliferation and mesenchymal transformation in pulmonary hypertension

  • 0College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
International Journal of Biological Macromolecules +

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June 29, 2024

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June 29, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

NF-E2-related factor 2 (NRF2) plays a dual role in pulmonary hypertension (PH). While reduced NRF2 promotes harmful cell changes in PH, its activation in smooth muscle cells may worsen PH by increasing cell proliferation and migration.

Area Of Science

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Signaling

Background

  • Pulmonary hypertension (PH) is a severe condition lacking effective treatments.
  • NF-E2-related factor 2 (NRF2) is crucial for cellular protection and was investigated in PH.
  • Understanding NRF2's role in pulmonary artery cells is key to developing new therapies.

Purpose Of The Study

  • To investigate NRF2 expression in PH models.
  • To elucidate NRF2's role in regulating pulmonary artery cell phenotypes.
  • To assess the potential therapeutic implications of NRF2 modulation in PH.

Main Methods

  • Examined NRF2 expression in lung tissues from PH models.
  • Analyzed NRF2 levels in rat pulmonary artery endothelial cells (rPAEC) and smooth muscle cells (rPASMC) under hypoxia.
  • Utilized siRNA and activators to study NRF2's effects on cell migration, proliferation, and specific molecular pathways.

Main Results

  • NRF2 expression was significantly decreased in PH lung tissues.
  • Hypoxia reduced NRF2 in rPAEC, promoting endothelial-mesenchymal transformation and reactive oxygen species.
  • Hypoxia increased NRF2 in rPASMC, accelerating migration (via MMP2/3/7) and proliferation (via PDGFR/ERK1/2, mTOR/P70S6K pathways).

Conclusions

  • NRF2 exhibits complex, cell-specific roles in pulmonary hypertension.
  • NRF2 activation in rPASMC may promote proliferation and migration, potentially exacerbating PH.
  • Clinical use of NRF2 activators for PH requires careful consideration of these side effects and combination therapies.

Keywords:

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