ArticleCardiovascular research2012
Hypoxia induces unique proliferative response in adventitial fibroblasts by activating PDGFβ receptor-JNK1 signalling.
Article in Cardiovascular research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- Purine synthesis suppression reduces the development and progression of pulmonary hypertension in rodent models.European heart journal · 2023Article
- Promising therapeutic mechanism for Chinese herbal medicine in ameliorating renal fibrosis in diabetic nephropathy.Frontiers in endocrinology · 2023Review
- The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude.Frontiers in cardiovascular medicine · 2022Review
- Inflammation in Pulmonary Arterial Hypertension.Advances in experimental medicine and biology · 2021Review
- Quantification of uncertainty in a new network model of pulmonary arterial adventitial fibroblast pro-fibrotic signalling.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2020Article
- Systemic arterial hypertension leads to decreased semen quality and alterations in the testicular microcirculation in rats.Scientific reports · 2019Article
- Hypoxia induces pulmonary arterial fibroblast proliferation, migration, differentiation and vascular remodeling via the PI3K/Akt/p70S6K signaling pathway.International journal of molecular medicine · 2018Article
- Translating Research into Improved Patient Care in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2017Review
- The JNK Signaling Pathway in Renal Fibrosis.Frontiers in physiology · 2017Review
- Article
- Microarray analysis in pulmonary hypertension.The European respiratory journal · 2016Review
- Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2016Article
- Leukotriene B4 Activates Pulmonary Artery Adventitial Fibroblasts in Pulmonary Hypertension.Hypertension (Dallas, Tex. : 1979) · 2015Article
- Metabolic reprogramming and inflammation act in concert to control vascular remodeling in hypoxic pulmonary hypertension.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Review
- The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- ROCK2 and MYLK variants under hypobaric hypoxic environment of high altitude associate with high altitude pulmonary edema and adaptation.The application of clinical genetics · 2015Article
- Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage phenotype in pulmonary hypertension.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Hypoxic response contributes to altered gene expression and precapillary pulmonary hypertension in patients with sickle cell disease.Circulation · 2014Article
- PK10453, a nonselective platelet-derived growth factor receptor inhibitor, prevents the progression of pulmonary arterial hypertension.Pulmonary circulation · 2014Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
aimsPulmonary hypertension (PH) is a devastating condition for which no disease-modifying therapies exist. PH is recognized as proliferative disease of the pulmonary artery (PA). In the experimental newborn calf model of hypoxia-induced PH, adventitial fibroblasts in the PA wall exhibit a heightened replication index. Because elevated platelet-derived growth factor β receptor (PDGFβ-R) signalling is associated with PH, we tested the hypothesis that the activation of PDGFβ-R contributes to fibroblast proliferation and adventitial remodelling in PH. METHODS AND
resultsNewborn calves were exposed to either ambient air (P(B) = 640 mmHg) (Neo-C) or high altitude (P(B) = 445 mm Hg) (Neo-PH) for 2 weeks. PDGFβ-R phosphorylation was markedly elevated in PA adventitia of Neo-PH calves as well as in cultured PA fibroblasts isolated from Neo-PH animals. PDGFβ-R activation with PDGF-BB stimulated higher replication in Neo-PH cells compared with that of control fibroblasts. PDGF-BB-induced proliferation was dependent on reactive oxygen species generation and extracellular signal-regulated kinase1/2 activation in both cell populations; however, only Neo-PH cell division via PDGFβ-R activation displayed a unique dependence on c-Jun N-terminal kinase1 (JNK1) stimulation as the blockade of JNK1 with SP600125, a pharmacological antagonist of the JNK pathway, and JNK1-targeted siRNA selectively blunted Neo-PH cell proliferation.
conclusionsOur data strongly suggest that hypoxia-induced modified cells engage the PDGFβ-R-JNK1 axis to confer distinctively heightened proliferation and adventitial remodelling in PH.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.