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

TitleSARS-CoV-2 receptor networks in diabetic and COVID-19-associated kidney disease.
Publication TypeJournal Article
Year of Publication2020
AuthorsMenon, R, Otto, EA, Sealfon, R, Nair, V, Wong, AK, Theesfeld, CL, Chen, X, Wang, Y, Boppana, AS, Luo, J, Yang, Y, Kasson, PM, Schaub, JA, Berthier, CC, Eddy, S, Lienczewski, CC, Godfrey, B, Dagenais, SL, Sohaney, R, Hartman, J, Fermin, D, Subramanian, L, Looker, HC, Harder, JL, Mariani, LH, Hodgin, JB, Sexton, JZ, Wobus, CE, Naik, AS, Nelson, RG, Troyanskaya, OG, Kretzler, M
JournalKidney Int
Date Published2020 Oct 08
ISSN1523-1755
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.

DOI10.1016/j.kint.2020.09.015
Alternate JournalKidney Int
PubMed ID33038424
PubMed Central IDPMC7543950
Grant ListUH3 DK114907 / DK / NIDDK NIH HHS / United States
P30 DK092926 / DK / NIDDK NIH HHS / United States
UH3 DK114923 / DK / NIDDK NIH HHS / United States
UH3 DK114908 / DK / NIDDK NIH HHS / United States
U2C DK114886 / DK / NIDDK NIH HHS / United States
UH3 DK114915 / DK / NIDDK NIH HHS / United States
UH3 DK114861 / DK / NIDDK NIH HHS / United States
P60 DK020572 / DK / NIDDK NIH HHS / United States
UH3 DK114866 / DK / NIDDK NIH HHS / United States
UH3 DK114870 / DK / NIDDK NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
P30 DK081943 / DK / NIDDK NIH HHS / United States
UH3 DK114933 / DK / NIDDK NIH HHS / United States
Z01 DK069062 / ImNIH / Intramural NIH HHS / United States
U54 DK083912 / DK / NIDDK NIH HHS / United States
UH3 DK114920 / DK / NIDDK NIH HHS / United States
R24 DK082841 / DK / NIDDK NIH HHS / United States
UH3 DK114926 / DK / NIDDK NIH HHS / United States
UH3 DK114937 / DK / NIDDK NIH HHS / United States