AI Article Synopsis
- Pulmonary artery hypertension (PAH) exhibits a metabolic shift towards aerobic glycolysis, resembling cancer metabolism, and involves the role of NSD2, though its exact function is not fully understood.
- Increased expression of FOLR1 in PAH tissues was linked to NSD2, and silencing either NSD2 or FOLR1 inhibited cell proliferation and the progression of PAH.
- The study found that NSD2 influences the activity of FOLR1, affecting glycolytic gene expression and metabolic processes in pulmonary artery endothelial cells, suggesting a potential pathway for therapeutic intervention in PAH.
Article Abstract
Pulmonary artery hypertension (PAH) is characterized by a cancer-like metabolic shift towards aerobic glycolysis. Nuclear Receptor Binding SET Domain Protein 2 (NSD2), a histone methyltransferase, has been implicated in PAH, yet its precise role remains unclear. In this study, we induced PAH in C57BL/6 mice using monocrotaline (MCT) and observed increased FOLR1 expression in PAH tissues, which was suppressed by NSD2 knockdown. Silencing NSD2 or FOLR1 inhibited the proliferation and migration of pulmonary artery endothelial cells (PAECs) and alleviated PAH phenotypes, right ventricular dysfunction, and pulmonary artery remodeling. Mechanistically, NSD2 knockdown prevented nuclear translocation of FOLR1 and its interaction with H3K36me2. Metabolic analysis revealed that NSD2 or FOLR1 knockdown reversed the increased oxygen consumption rate, extracellular acidification rate, glucose consumption, lactate production, and G6PD activity in MCT-treated PAECs. Furthermore, NSD2 or FOLR1 silencing decreased the expression of key glycolytic genes (HK2, TIGAR, and G6PD) by suppressing their promoter activity and weakening the interaction between FOLR1/H3K36me2 and these gene promoters. Our findings suggest that NSD2-mediated H3K36me2 recruits FOLR1 to promote PAH, and FOLR1 acts as a transcriptional factor to upregulate glycolytic gene expression in PAECs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cellsig.2025.111594 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efficacy and safety of single-branched stent graft in the treatment of type B aortic dissection: a meta-analysis of cohort studies.
J Cardiothorac Surg
January 2025
Department of Vascular Surgery, Zhangzhou Affiliated Hospital of FuJian Medical University, Zhangzhou, Fujian Province, 363000, China.
Background: Thoracic aortic endovascular repair (TEVAR) is the most commonly employed method for treating type B aortic dissection (TBAD). One of the primary challenges in TEVAR is the reconstruction of the left subclavian artery (LSA). Various revascularization strategies have been utilized, including branch stent techniques, fenestration techniques, chimney techniques, and hybrid techniques.
View Article and Find Full Text PDFDifferential substrate specificity of ERK, JNK, and p38 MAP kinases toward Connexin 43.
J Biol Chem
January 2025
Department of Biological Sciences, Moravian University, 1200 Main Street, Bethlehem, PA 18018, USA. Electronic address:
Phosphorylation of connexin 43 (Cx43) is an important regulatory mechanism of gap junction (GJ) function. Cx43 is modified by several kinases on over 15 sites within its ∼140 amino acid-long C-terminus (CT). Phosphorylation of Cx43CT on S255, S262, S279, and S282 by ERK has been widely documented in several cell lines, by many investigators.
View Article and Find Full Text PDFNSD2 mediated H3K36me2 promotes pulmonary arterial hypertension by recruiting FOLR1 and metabolism reprogramming.
Cell Signal
January 2025
Department of Cardiovascular Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China. Electronic address:
Article Synopsis
- Pulmonary artery hypertension (PAH) exhibits a metabolic shift towards aerobic glycolysis, resembling cancer metabolism, and involves the role of NSD2, though its exact function is not fully understood.
- Increased expression of FOLR1 in PAH tissues was linked to NSD2, and silencing either NSD2 or FOLR1 inhibited cell proliferation and the progression of PAH.
- The study found that NSD2 influences the activity of FOLR1, affecting glycolytic gene expression and metabolic processes in pulmonary artery endothelial cells, suggesting a potential pathway for therapeutic intervention in PAH.
Potential role of TRAF2 in pulmonary hypertension in broiler chickens and preparation and specificity analysis of its polyclonal antibody.
Int J Biol Macromol
January 2025
College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, 330045, PR China. Electronic address:
Due to the lack of specific antibody anti-chicken tumor necrosis factor receptor-associated factor 2 (TRAF2), it is difficult to further explore the role of TRAF2 in pulmonary artery remodeling in pulmonary hypertension(PH) in broilers. In this experiment, we prepared a polyclonal antibody to TRAF2 by constructing a TRAF2 recombinant protein prokaryotic expression vector and analyzed the expression of TRAF2 in in vivo and in vitro models of pulmonary hypertension in broiler chickens and the effect of TRAF2 on the activity and apoptosis of PASMCs. The results showed that after immunization with TRAF2 recombinant protein we obtained high titers of polyclonal antibodies, and astragalus polysaccharide as an immune adjuvant could enhance the effect of immunization.
View Article and Find Full Text PDFReduced contrast agent volume using a heart-rate dependent and free-breathing scanning protocol in coronary computed tomography angiography (CTA) for patients with chronic obstructive pulmonary disease (COPD).
BMC Cardiovasc Disord
January 2025
Department of Radiology, Central Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province, China.
Background: The personalized, free-breathing, heart rate-dependent computed tomography angiography (CTA) protocol can significantly reduce the utilization of contrast medium (CM). This proves especially beneficial for patients with chronic obstructive pulmonary disease (COPD) undergoing coronary artery CTA examinations.
Objective: The aim of this study was to evaluate the feasibility of a personalized CT scanning protocol that was tailored to patients' heart rate and free-breathing for coronary CTA of patients with COPD.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!