دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: The mechanism of NRF2 regulating cell proliferation and mesenchymal transformation in pulmonary hypertension.
المؤلفون: Ning S; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: 15835483104@163.com., Guo X; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: gxyxinyue@163.com., Zhu Y; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: zhuyanan1999@nwafu.edu.cn., Li C; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: lch0128@nwafu.edu.cn., Li R; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: yuanyuanyyhh@yeah.net., Meng Y; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: myn186019@nwafu.edu.cn., Luo W; Military Mental Cognition, Strategic Support Force Medical Center, No. 9 Anxiangbeili, Chaoyang District, Beijing 100101, China. Electronic address: luoweiwei@bjmu.edu.cn., Lu D; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: dezhanglu@nwsuaf.edu.cn., Yin Y; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: yupeng@nwafu.edu.cn.
المصدر: International journal of biological macromolecules [Int J Biol Macromol] 2024 Aug; Vol. 275 (Pt 1), pp. 133514. Date of Electronic Publication: 2024 Jun 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: Guildford, Eng., IPC Science and Technology Press.
مواضيع طبية MeSH: NF-E2-Related Factor 2*/metabolism , NF-E2-Related Factor 2*/genetics , Hypertension, Pulmonary*/metabolism , Hypertension, Pulmonary*/genetics , Hypertension, Pulmonary*/pathology , Cell Proliferation* , Cell Movement* , Pulmonary Artery*/metabolism , Pulmonary Artery*/pathology, Animals ; Rats ; Myocytes, Smooth Muscle/metabolism ; Reactive Oxygen Species/metabolism ; Endothelial Cells/metabolism ; Male ; Signal Transduction ; Epithelial-Mesenchymal Transition/genetics ; Rats, Sprague-Dawley ; Disease Models, Animal
مستخلص: 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.
Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Endothelial-mesenchymal transformation; Migration; NF-E2-related factor 2; Proliferation; Pulmonary hypertension
المشرفين على المادة: 0 (NF-E2-Related Factor 2)
0 (Reactive Oxygen Species)
0 (Nfe2l2 protein, rat)
تواريخ الأحداث: Date Created: 20240629 Date Completed: 20240808 Latest Revision: 20240808
رمز التحديث: 20240808
DOI: 10.1016/j.ijbiomac.2024.133514
PMID: 38944076
قاعدة البيانات: MEDLINE