2. Academic Validation
  3. The mechanism of NRF2 regulating cell proliferation and mesenchymal transformation in pulmonary hypertension

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

  • Int J Biol Macromol. 2024 Jun 27;275(Pt 1):133514. doi: 10.1016/j.ijbiomac.2024.133514.
Shasha Ning 1,  Xinyue Guo 2,  Yanan Zhu 3,  Chenghui Li 4,  Ruixue Li 5,  Yinan Meng 6,  Weiwei Luo 7,  Dezhang Lu 8,  Yupeng Yin 9
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: 15835483104@163.com.
  • 2 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: gxyxinyue@163.com.
  • 3 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: zhuyanan1999@nwafu.edu.cn.
  • 4 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: lch0128@nwafu.edu.cn.
  • 5 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: yuanyuanyyhh@yeah.net.
  • 6 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: myn186019@nwafu.edu.cn.
  • 7 Military Mental Cognition, Strategic Support Force Medical Center, No. 9 Anxiangbeili, Chaoyang District, Beijing 100101, China. Electronic address: luoweiwei@bjmu.edu.cn.
  • 8 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: dezhanglu@nwsuaf.edu.cn.
  • 9 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: yupeng@nwafu.edu.cn.
PMID: 38944076 DOI: 10.1016/j.ijbiomac.2024.133514
Abstract

Pulmonary hypertension (PH) is a fatal disease with no existing curative drugs. NF-E2-related factor 2 (NRF2) a pivotal molecular in cellular protection, was investigated in PH models to elucidate its role in regulating abnormal phenotypes in pulmonary artery cells. We examined the expression of NRF2 in PH models and explored the role of NRF2 in regulating abnormal phenotypes in pulmonary artery cells. We determined the expression level of NRF2 in lung tissues of PH model decreased significantly. We found that NRF2 was reduced in rat pulmonary artery endothelial cells (rPAEC) under hypoxia, while it was overexpressed in rat pulmonary artery smooth muscle cells (rPASMC) under hypoxia. Next, the results showed that knockdown NRF2 in rPAEC promoted endothelial-mesenchymal transformation and upregulated Reactive Oxygen Species level. After the rPASMC was treated with siRNA or activator, we found that NRF2 could accelerate cell migration by affecting MMP2/3/7, and promote cell proliferation by regulating PDGFR/ERK1/2 and mTOR/p70S6K pathways. Therefore, the study has shown that the clinical application of NRF2 activator in the treatment of pulmonary hypertension may cause side effects of promoting the proliferation and migration of rPASMC. Attention should be paid to the combination of NRF2 activators.

Keywords

Endothelial-mesenchymal transformation; Migration; NF-E2-related factor 2; Proliferation; Pulmonary hypertension.

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