ArticleAmerican journal of physiology. Lung cellular and molecular physiology2009
Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia.
Article in American journal of physiology. Lung cellular and molecular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
227 citing papers in PubMed, 3 syntheses or guidelines pooled it, 345 citations in OpenAlex.
- The effects of vitamin D on all-cause mortality in different diseases: an evidence-map and umbrella review of 116 randomized controlled trials.Frontiers in nutrition · 2023Pooled it
- Pooled it
- ACE2 Expression Is Increased in the Lungs of Patients With Comorbidities Associated With Severe COVID-19.The Journal of infectious diseases · 2020Pooled it
- Temporal changes in soluble angiotensin-converting enzyme 2 associated with metabolic health, body composition, and proteome dynamics during a weight loss diet intervention: a randomized trial with implications for the COVID-19 pandemic.The American journal of clinical nutrition · 2021Trial
- A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure.American journal of physiology. Lung cellular and molecular physiology · 2021Trial
- Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation.European heart journal · 2020Trial
- The balance between classical and alternative renin-angiotensin system in ARDS: a narrative review.Journal of intensive care · 2026Review
- Fecal ACE and ACE2 Activities Reflect Intestinal Shedding and Microbiota Modulation of Renin-Angiotensin System.Biology · 2026Article
- The Role of ACE2 in SARS-CoV-2 Infection, Pathogenesis, and Antiviral Interventions.Journal of medical virology · 2025Review
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Integrated renin angiotensin system dysregulation and immune profiles predict COVID-19 disease severity in a South African cohort.Scientific reports · 2025Article
- Vasoactive Intestinal Peptide (VIP) in COVID-19 Therapy-Shedding of ACE2 and TMPRSS2 via ADAM10.International journal of molecular sciences · 2025Article
- Article
- Restoring lung renin-angiotensin system balance through blood pressure control.Clinical science (London, England : 1979) · 2025Article
- Circulating angiotensin-converting enzyme 2 concentration is associated with acute kidney injury and mortality in sepsis.PloS one · 2025Article
- Dual role of ACE2 in regulating inflammation triggered by Omicron S1 and other SARS-CoV-2 Spike variants.Frontiers in immunology · 2025Article
- Recombinant ACE2 - Opportunities and Challenges in COVID-19 Treatment.Infectious disorders drug targets · 2025Review
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- The Evaluation of Drugs as Potential Modulators of the Trafficking and Maturation of ACE2, the SARS-CoV-2 Receptor.Biomolecules · 2024Article
- tANCHOR-cell-based assay for monitoring of SARS-CoV-2 neutralizing antibodies rapidly adaptive to various receptor-binding domains.iScience · 2024Article
167 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Angiotensin-converting enzyme 2 (ACE2) is a terminal carboxypeptidase and the receptor for the SARS and NL63 coronaviruses (CoV). Loss of ACE2 function is implicated in severe acute respiratory syndrome (SARS) pathogenesis, but little is known about ACE2 biogenesis and activity in the airways. We report that ACE2 is shed from human airway epithelia, a site of SARS-CoV infection. The regulation of ACE2 release was investigated in polarized human airway epithelia. Constitutive generation of soluble ACE2 was inhibited by DPC 333, implicating a disintegrin and metalloprotease 17 (ADAM17). Phorbol ester, ionomycin, endotoxin, and IL-1beta and TNFalpha acutely induced ACE2 release, further supporting that ADAM17 and ADAM10 regulate ACE2 cleavage. Soluble ACE2 was enzymatically active and partially inhibited virus entry into target cells. We determined that the ACE2 cleavage site resides between amino acid 716 and the putative transmembrane domain starting at amino acid 741. To reveal structural determinants underlying ACE2 release, several mutant and chimeric ACE2 proteins were engineered. Neither the juxtamembrane stalk region, transmembrane domain, nor the cytosolic domain was needed for constitutive ACE2 release. Interestingly, a point mutation in the ACE2 ectodomain, L584A, markedly attenuated shedding. The resultant ACE2-L584A mutant trafficked to the cell membrane and facilitated SARS-CoV entry into target cells, suggesting that the ACE2 ectodomain regulates its release and that residue L584 might be part of a putative sheddase "recognition motif." Thus ACE2 must be cell associated to serve as a CoV receptor and soluble ACE2 might play a role in modifying inflammatory processes at the airway mucosal surface.
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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.