ArticleRespiratory research2022
Notch4 mediates vascular remodeling via ERK/JNK/P38 MAPK signaling pathways in hypoxic pulmonary hypertension.
Article in Respiratory research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- GLSP ameliorates monocrotaline-induced pulmonary arterial hypertension through inhibition of the PI3K/AKT and MAPK signaling pathways.Journal of molecular histology · 2026Article
- Gain of function NOTCH4 variants disrupt angiogenesis in systemic sclerosis.Annals of the rheumatic diseases · 2026Article
- Serum Pharmacochemistry-Guided DARTS-MS Profiling Reveals Potential Mechanisms ofInternational journal of molecular sciences · 2026Article
- Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets.Cell proliferation · 2026Review
- HBiomedicines · 2026Article
- Short tandem repeats in populations of the Qinghai-Tibet Plateau and adjacent regions provide insights into high-altitude adaptation.Science advances · 2025Article
- [Mechanism of Trifolin in Attenuating Hypertension-Induced Renal Cell Apoptosis via Modulation of the MAPK Signaling Pathway].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Silencing PPAP2C inhibits lung adenocarcinoma migration and invasion via the ERK/JNK pathway.Molecular medicine reports · 2025Article
- Bronchial anastomotic complications as a microvascular disruption in a mouse model of airway transplantation.Frontiers in immunology · 2025Review
- Effects of sildenafil and metformin on endothelin-1 in the progression of pulmonary hypertension.Open veterinary journal · 2025Article
- Elevated Shear Stress Modulates Heterogenous Cellular Subpopulations to Induce Vascular Remodeling.Tissue engineering. Part A · 2024Article
- CC chemokines Modulate Immune responses in Pulmonary Hypertension.Journal of advanced research · 2024Review
- Differential expression and analysis of extrachromosomal circular DNAs as serum biomarkers in pulmonary arterial hypertension.Respiratory research · 2024Article
- Up-regulated expression of two-pore domain KFrontiers in cardiovascular medicine · 2024Article
- Early short-term hypoxia promotes epidermal cell migration by activating the CCL2-ERK1/2 pathway and epithelial-mesenchymal transition during wound healing.Burns & trauma · 2024Article
- Insights into Endothelin Receptors in Pulmonary Hypertension.International journal of molecular sciences · 2023Review
- Gut Microbiota and Metabolome Changes in Three Pulmonary Hypertension Rat Models.Microorganisms · 2023Article
- Neurodevelopmental and genetic findings in neonates with intracranial arteriovenous shunts: A case series.Frontiers in pediatrics · 2023Article
- Ginkgolide B Blocks Vascular Remodeling after Vascular Injury via Regulating TgfCardiovascular therapeutics · 2023Article
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11 authors.
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Abstract
backgroundHypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling.
methodsLung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated.
resultsIn this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats.
conclusionsThese findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.
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