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SARS-CoV-2 receptor networks in diabetic and COVID-19-associated kidney disease.
- Source :
-
Kidney international [Kidney Int] 2020 Dec; Vol. 98 (6), pp. 1502-1518. Date of Electronic Publication: 2020 Oct 08. - Publication Year :
- 2020
-
Abstract
- 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.<br /> (Copyright © 2020 International Society of Nephrology. All rights reserved.)
- Subjects :
- Adult
Aged
Angiotensin Receptor Antagonists pharmacology
Angiotensin Receptor Antagonists therapeutic use
Angiotensin-Converting Enzyme Inhibitors pharmacology
Angiotensin-Converting Enzyme Inhibitors therapeutic use
COVID-19 complications
COVID-19 virology
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
Angiotensin-Converting Enzyme 2 metabolism
COVID-19 metabolism
Diabetic Nephropathies metabolism
Kidney Tubules, Proximal metabolism
SARS-CoV-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1755
- Volume :
- 98
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 33038424
- Full Text :
- https://doi.org/10.1016/j.kint.2020.09.015