ArticlePediatric research2015
Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts.
Article in Pediatric research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- Screening for biomarkers of bronchopulmonary dysplasia: a bioinformatics analysis.Translational pediatrics · 2025Article
- Alveolar Hyperoxia and Exacerbation of Lung Injury in Critically Ill SARS-CoV-2 Pneumonia.Medical sciences (Basel, Switzerland) · 2023Review
- Unraveling the Underlying Molecular Mechanism of 'Silent Hypoxia' in COVID-19 Patients Suggests a Central Role for Angiotensin II Modulation of the AT1R-Hypoxia-Inducible Factor Signaling Pathway.Journal of clinical medicine · 2023Review
- Influence of weather factors on the incidence of COVID-19 in Spain.Medicina clinica (English ed.) · 2022Article
- Influence of weather factors on the incidence of COVID-19 in Spain.Medicina clinica · 2022Article
- Clinical characteristics and mortality associated with COVID-19 at high altitude: a cohort of 5161 patients in Bogotá, Colombia.International journal of emergency medicine · 2022Article
- The impact of COVID-19 on populations living at high altitude: Role of hypoxia-inducible factors (HIFs) signaling pathway in SARS-CoV-2 infection and replication.Frontiers in physiology · 2022Article
- An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection.Frontiers in microbiology · 2022Review
- The Association of Renin-Angiotensin System Blockades and Mortality in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Acute Respiratory Failure: A Retrospective Cohort Study.International journal of chronic obstructive pulmonary disease · 2022Article
- The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia.Frontiers in immunology · 2022Review
- Alternative RAS in Various Hypoxic Conditions: From Myocardial Infarction to COVID-19.International journal of molecular sciences · 2021Review
- The Immunopathobiology of SARS-CoV-2 Infection.FEMS microbiology reviews · 2021Article
- Interplay between hypoxia and inflammation contributes to the progression and severity of respiratory viral diseases.Molecular aspects of medicine · 2021Review
- Genetic and epigenetic control of ACE2 expression and its possible role in COVID-19.Cell biochemistry and function · 2021Review
- COVID-19 and developmental origins of health and disease.Early human development · 2021Review
- Angiotensin Converting Enzyme-2 (ACE-2) role in disease and future in research.Journal of lung, pulmonary & respiratory research · 2021Article
- COVID-19-A Theory of Autoimmunity Against ACE-2 Explained.Frontiers in immunology · 2021Review
- Clinical and Laboratory Findings of COVID-19 in High-Altitude Inhabitants of Saudi Arabia.Frontiers in medicine · 2021Article
- Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients.Frontiers in cellular and infection microbiology · 2021Article
- Regulation of ACE-2 enzyme by hyperoxia in lung epithelial cells by post-translational modification.Journal of lung, pulmonary & respiratory research · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAngiotensin (ANG) II is involved in experimental hyperoxia-induced lung fibrosis. Angiotensin-converting enzyme-2 (ACE-2) degrades ANG II and is thus protective, but is downregulated in adult human and experimental lung fibrosis. Hyperoxia is a known cause of chronic fibrotic lung disease in neonates, but the role of ACE-2 in neonatal lung fibrosis is unknown. We hypothesized that ACE-2 in human fetal lung cells might be downregulated by hyperoxic gas.
methodsFetal human lung fibroblast IMR90 cells were exposed to hyperoxic (95% O2/5% CO2) or normoxic (21% O2/5% CO2) gas in vitro. Cells and culture media were recovered separately for assays of ACE-2 enzymatic activity, mRNA, and immunoreactive protein.
resultsHyperoxia decreased ACE-2 immunoreactive protein and enzyme activity in IMR90 cells (both P < 0.01), but did not change ACE-2 mRNA. ACE-2 protein was increased in the cell supernatant, suggesting protease-mediated ectodomain shedding. TAPI-2, an inhibitor of TNF-α-converting enzyme (TACE/ADAM17), prevented both the decrease in cellular ACE-2 and the increase in soluble ACE-2 (both P < 0.05).
conclusionThese data show that ACE-2 is expressed in fetal human lung fibroblasts but is significantly decreased by hyperoxic gas. They also suggest that hyperoxia decreases ACE-2 through a shedding mechanism mediated by ADAM17/TACE.
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