ArticleAmerican journal of respiratory cell and molecular biology2016
Activation of Calpain-2 by Mediators in Pulmonary Vascular Remodeling of Pulmonary Arterial Hypertension.
Article in American journal of respiratory cell and molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Tryptophan metabolism: a potential link between the gut microbiota and pulmonary vascular remodeling in pulmonary hypertension.Frontiers in cellular and infection microbiology · 2026Review
- Neutrophil elastase activates macrophage calpain as a mechanism for phagocytic failure.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- 5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase promotes pulmonary arterial smooth muscle cell proliferation via the Ras signaling pathway.American journal of physiology. Cell physiology · 2024Article
- Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1α signaling pathway.Cellular and molecular life sciences : CMLS · 2024Article
- Prime editing in mice with an engineered pegRNA.Vascular pharmacology · 2024Article
- Calpain Promotes LPS-induced Lung Endothelial Barrier Dysfunction via Cleavage of Talin.American journal of respiratory cell and molecular biology · 2023Article
- Biallelic variants in the calpain regulatory subunitGenetics in medicine open · 2023Article
- Signal Transduction during Metabolic and Inflammatory Reprogramming in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2022Review
- HDAC6 Activates ERK in Airway and Pulmonary Vascular Remodeling of Chronic Obstructive Pulmonary Disease.American journal of respiratory cell and molecular biology · 2021Article
- HDAC6: A Neglected Player in Chronic Obstructive Pulmonary Disease?American journal of respiratory cell and molecular biology · 2021Article
- Endothelial upregulation of mechanosensitive channel Piezo1 in pulmonary hypertension.American journal of physiology. Cell physiology · 2021Article
- MicroRNA-137 Inhibited Hypoxia-Induced Proliferation of Pulmonary Artery Smooth Muscle Cells by Targeting Calpain-2.BioMed research international · 2021Article
- Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia.Pediatric research · 2020Article
- Reactive Oxygen Species-Dependent Calpain Activation Contributes to Airway and Pulmonary Vascular Remodeling in Chronic Obstructive Pulmonary Disease.Antioxidants & redox signaling · 2019Article
- PFKFB3 in Smooth Muscle Promotes Vascular Remodeling in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2019Article
- Anti-Remodeling Effects of Xanthohumol-Fortified Beer in Pulmonary Arterial Hypertension Mediated by ERK and AKT Inhibition.Nutrients · 2019Article
- BMP4 inhibits PDGF-induced proliferation and collagen synthesis via PKA-mediated inhibition of calpain-2 in pulmonary artery smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Redox-Dependent Calpain Signaling in Airway and Pulmonary Vascular Remodeling in COPD.Advances in experimental medicine and biology · 2017Article
- The inhibition of calpains ameliorates vascular restenosis through MMP2/TGF-β1 pathway.Scientific reports · 2016Article
- Calpain-2 activates Akt via TGF-β1-mTORC2 pathway in pulmonary artery smooth muscle cells.American journal of physiology. Cell physiology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
Calpain mediates collagen synthesis and cell proliferation and plays an important role in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). In the present study, we investigated whether and how calpain is activated by PAH mediators in pulmonary artery smooth muscle cells (PASMCs). These data show that smooth muscle-specific knockout of calpain attenuated and knockout of calpastatin potentiated pulmonary vascular remodeling and pulmonary hypertension. Treatment of PASMCs with the PAH mediators platelet-derived growth factor (PDGF), serotonin, H2O2, endothelin-1, and IL-6 caused significant increases in calpain activity, cell proliferation, and collagen-I protein level without changes in protein levels of calpain-1 and -2. The calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA/AM) did not affect calpain activation, but the extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 and knocking down of calpain-2 prevented calpain activation in PAH mediator-treated PASMCs. Mass spectrometry data showed that the phosphorylation of calpain-2 at serine (Ser) 50 was increased and the phosphorylation of calpain-2 at Ser369 was decreased in PDGF-treated PASMCs. The PDGF-induced increase in Ser50 phosphorylation of calpain-2 was prevented by PD98059, whereas dephosphorylation of calpain-2 at Ser369 was blocked by the protein phosphatase 2A inhibitor fostriecin. Furthermore, smooth muscle of pulmonary arteries in PAH animal models and patients with PAH showed higher levels of phospho-Ser50-calpain-2 (P-Ser50) and lower levels of phospho-Ser369-calpain-2 (P-Ser369). These data support that calpain modulates pulmonary vascular remodeling in PAH. PAH mediator-induced activation of calpain is caused by ERK1/2-dependent phosphorylation of calpain-2 at Ser50 and protein phosphatase 2A-dependent dephosphorylation of calpain-2 at Ser369 in pulmonary vascular remodeling of PAH.
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