ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
PKC δ and βII regulate angiotensin II-mediated fibrosis through p38: a mechanism of RV fibrosis in pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Computational modeling identifies protective mechanisms of estrogen and testosterone against atrial fibrosis.American journal of physiology. Heart and circulatory physiology · 2026Article
- Computational modelling of cardiac fibroblast signalling reveals a key role for CaThe Journal of physiology · 2025Article
- Inhibition of PKC-δ retards kidney fibrosis via inhibiting cGAS-STING signaling pathway in mice.Cell death discovery · 2024Article
- Endoplasmic reticulum stress contributes to cisplatin-induced chronic kidney disease via the PERK-PKCδ pathway.Cellular and molecular life sciences : CMLS · 2022Article
- Research Progress on Pulmonary Arterial Hypertension and the Role of the Angiotensin Converting Enzyme 2-Angiotensin-(1-7)-Mas Axis in Pulmonary Arterial Hypertension.Cardiovascular drugs and therapy · 2022Review
- Angiotensin II type 1 receptor mediates pulmonary hypertension and right ventricular remodeling induced by inhaled nicotine.American journal of physiology. Heart and circulatory physiology · 2021Article
- PKCβ/NF-κB pathway in diabetic atrial remodeling.Journal of physiology and biochemistry · 2020Article
- Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia.International journal of molecular sciences · 2020Review
- Computational model predicts paracrine and intracellular drivers of fibroblast phenotype after myocardial infarction.Matrix biology : journal of the International Society for Matrix Biology · 2020Review
- Treatment of Pulmonary Hypertension With Angiotensin II Receptor Blocker and Neprilysin Inhibitor Sacubitril/Valsartan.Circulation. Heart failure · 2019Article
- Role of phospholipase D in bleomycin-induced mitochondrial reactive oxygen species generation, mitochondrial DNA damage, and pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
- Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension.Frontiers in cardiovascular medicine · 2018Review
- Effect of α7 nicotinic acetylcholine receptor activation on cardiac fibroblasts: a mechanism underlying RV fibrosis associated with cigarette smoke exposure.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Update on novel targets and potential treatment avenues in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Transcriptional control of cardiac fibroblast plasticity.Journal of molecular and cellular cardiology · 2016Review
- Endurance exercise training in pulmonary hypertension increases skeletal muscle electron transport chain supercomplex assembly.Pulmonary circulationArticle
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Pulmonary hypertension (PH) eventually leads to right ventricular (RV) fibrosis and dysfunction that is associated with increased morbidity and mortality. Although angiotensin II plays an important role in RV remodeling associated with hypoxic PH, the molecular mechanisms underlying RV fibrosis in PH largely remain unresolved. We hypothesized that PKC-p38 signaling is involved in RV collagen accumulation in PH and in response to angiotensin II stimulation. Adult male Sprague-Dawley rats were exposed to 3 wk of normoxia or hypoxia (10% FiO2 ) as a model of PH. Hypoxic rats developed RV hypertrophy and fibrosis associated with an increase in PKC βII and δ protein expression and p38 dephosphorylation in freshly isolated RV cardiac fibroblasts. Further mechanistic studies were performed in cultured primary cardiac fibroblasts stimulated with angiotensin II, a key activator of ventricular fibrosis in PH. Angiotensin II induced a reduction in p38 phosphorylation that was attenuated following chemical inhibition of PKC βII and δ. Molecular and chemical inhibition of PKC βII and δ abrogated angiotensin II-induced cardiac fibroblast proliferation and collagen deposition in vitro. The effects of PKC inhibition on proliferation and fibrosis were reversed by chemical inhibition of p38. Conversely, constitutive activation of p38 attenuated angiotensin II-induced increase of cardiac fibroblast proliferation and collagen accumulation. PKC βII- and δ-dependent inactivation of p38 regulates cardiac fibroblast proliferation and collagen deposition in response to angiotensin II, which suggests that the PKC-p38 signaling in cardiac fibroblasts may be involved and important in the pathophysiology of RV fibrosis in PH.
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