SARS-CoV-2 receptor networks in diabetic and COVID-19-associated kidney disease.

Adult Aged Angiotensin Receptor Antagonists / pharmacology Angiotensin-Converting Enzyme 2 / metabolism Angiotensin-Converting Enzyme Inhibitors / pharmacology COVID-19 / complications Case-Control Studies Diabetic Nephropathies / drug therapy Female Gene Expression Profiling Gene Regulatory Networks Host-Pathogen Interactions Humans Kidney Tubules, Proximal / drug effects Male Middle Aged SARS-CoV-2 / metabolism
ACE inhibitors COVID-19 SARS-CoV-2 acute kidney injury diabetic nephropathy molecular networks proximal tubules scRNAseq

Journal

Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470

Informations de publication

Date de publication:
12 2020
Historique:
received: 25 06 2020
revised: 01 09 2020
accepted: 03 09 2020
pubmed: 11 10 2020
medline: 22 12 2020
entrez: 10 10 2020
Statut: ppublish

Résumé

COVID-19 morbidity and mortality are increased via unknown mechanisms in patients with diabetes and kidney disease. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Because ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease and medications alter ACE2 receptor expression in kidneys. Single cell RNA profiling of kidney biopsies from healthy living donors and patients with diabetic kidney disease revealed ACE2 expression primarily in proximal tubular epithelial cells. This cell-specific localization was confirmed by in situ hybridization. ACE2 expression levels were unaltered by exposures to renin-angiotensin-aldosterone system inhibitors in diabetic kidney disease. Bayesian integrative analysis of a large compendium of public -omics datasets identified molecular network modules induced in ACE2-expressing proximal tubular epithelial cells in diabetic kidney disease (searchable at hb.flatironinstitute.org/covid-kidney) that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. The diabetic kidney disease ACE2-positive proximal tubular epithelial cell module overlapped with expression patterns seen in SARS-CoV-2-infected cells. Similar cellular programs were seen in ACE2-positive proximal tubular epithelial cells obtained from urine samples of 13 hospitalized patients with COVID-19, suggesting a consistent ACE2-coregulated proximal tubular epithelial cell expression program that may interact with the SARS-CoV-2 infection processes. Thus SARS-CoV-2 receptor networks can seed further research into risk stratification and therapeutic strategies for COVID-19-related kidney damage.

Identifiants

DOI: 10.1016/j.kint.2020.09.015 PMID: 33038424 PMC: PMC7543950
pubmed: 33038424
pii: S0085-2538(20)31113-3
doi: 10.1016/j.kint.2020.09.015
pmc: PMC7543950
pii:
doi:

Substances chimiques

Angiotensin Receptor Antagonists 0
Angiotensin-Converting Enzyme Inhibitors 0
ACE2 protein, human EC 3.4.17.23
Angiotensin-Converting Enzyme 2 EC 3.4.17.23

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1502-1518

Subventions

Organisme : NIDDK NIH HHS
ID : UH3 DK114907
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK092926
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114923
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114908
Pays : United States
Organisme : NIDDK NIH HHS
ID : U2C DK114886
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114915
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114861
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007378
Pays : United States
Organisme : NIDDK NIH HHS
ID : P60 DK020572
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114866
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002240
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK081943
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114933
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 DK069062
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK114886
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK083912
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114920
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK082841
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114926
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114937
Pays : United States
Organisme : NIDDK NIH HHS
ID : UH3 DK114870
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK114907
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

Copyright © 2020 International Society of Nephrology. All rights reserved.

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Auteurs

Rajasree Menon (R)

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.

Edgar A Otto (EA)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Rachel Sealfon (R)

Center for Computational Biology, Flatiron Institute, New York, New York, USA.

Viji Nair (V)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Aaron K Wong (AK)

Center for Computational Biology, Flatiron Institute, New York, New York, USA.

Chandra L Theesfeld (CL)

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.

Xi Chen (X)

Center for Computational Biology, Flatiron Institute, New York, New York, USA.

Yuan Wang (Y)

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA; Department of Computer Science, Princeton University, Princeton, New Jersey, USA.

Avinash S Boppana (AS)

Department of Computer Science, Princeton University, Princeton, New Jersey, USA.

Jinghui Luo (J)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Yingbao Yang (Y)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Peter M Kasson (PM)

Departments of Molecular Physiology and Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.

Jennifer A Schaub (JA)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Celine C Berthier (CC)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Sean Eddy (S)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Chrysta C Lienczewski (CC)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Bradley Godfrey (B)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Susan L Dagenais (SL)

Advanced Genomics Core, Biomedical Research Core Facility, University of Michigan, Ann Arbor, Michigan, USA.

Ryann Sohaney (R)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

John Hartman (J)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Damian Fermin (D)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Lalita Subramanian (L)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Helen C Looker (HC)

Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.

Jennifer L Harder (JL)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Laura H Mariani (LH)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Jeffrey B Hodgin (JB)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Jonathan Z Sexton (JZ)

Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA.

Christiane E Wobus (CE)

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.

Abhijit S Naik (AS)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA.

Robert G Nelson (RG)

Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.

Olga G Troyanskaya (OG)

Center for Computational Biology, Flatiron Institute, New York, New York, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA; Department of Computer Science, Princeton University, Princeton, New Jersey, USA. Electronic address: ogt@cs.princeton.edu.

Matthias Kretzler (M)

Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: kretzler@umich.edu.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antagonistes des récepteurs aux angiotensines › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Exopeptidases › Carboxypeptidases › Angiotensin-converting enzyme 2 › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéases › Inhibiteurs de l'enzyme de conversion de l'angiotensine › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Complications du diabète › Néphropathies diabétiques › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Séquences d'acides nucléiques régulatrices › Réseaux de régulation génique › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Phénomènes biologiques › Interactions hôte-microbes › Interactions hôte-pathogène › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Néphrons › Tubules rénaux › Tubules contournés proximaux › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › SARS-CoV-2 receptor networks in diabetic and...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › SARS-CoV-2 receptor networks in diabetic and...