Corpus overview


Overview

MeSH Disease

HGNC Genes

Transmission

There are no transmission terms in the subcorpus


Seroprevalence

There are no seroprevalence terms in the subcorpus

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    SARS-CoV-2 receptor networks in diabetic kidney disease MESHD, BK-Virus nephropathy MESHD and COVID-19 MESHD associated acute kidney injury MESHD

    Authors: Rajasree Menon; Edgar A Otto; Rachel Sealfon; Viji Nair; Aaron K Wong; Chandra L Theesfeld; Xi Chen; Yuan Wang; Avinash Boppanna; Peter M Kasson; Jennifer A Schaub; Celine C Berthier; Sean Eddy; Chrysta C Lienczewski; Bradley Godfrey; Susan L Dagenais; Ryann Sohaney; John Hartman; Damian Fermin; Lalita Subramanian; Helen C Looker; Laura H Mariani; Abhijit S Naik; Robert G Nelson; Olga G. Troyanskaya; Matthias Kretzler

    doi:10.1101/2020.05.09.20096511 Date: 2020-05-13 Source: medRxiv

    COVID-19 MESHD morbidity and mortality is significantly increased in patients with diabetes MESHD and kidney disease MESHD via unknown mechanisms. SARS-CoV-2 uses angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) for entry into human host cells, and ACE2 HGNC levels in target cells may influence SARS-CoV-2 susceptibility. We investigated how pre-existing conditions and drug treatments alter receptor expression in kidney tissue. Using single cell RNA profiling (scRNAseq) to assess ACE2 HGNC and associated SARS-CoV-2 proteases in healthy living donors (LD) kidneys, diabetic kidney disease MESHD ( DKD MESHD), and in kidney injury MESHD during viral infection MESHD, ACE2 HGNC expression was primarily associated with proximal tubular epithelial cells (PTEC). ACE2 HGNC mRNA expression levels were significantly upregulated in DKD MESHD versus LD, however, ACE2 HGNC levels were not altered by exposures to renin HGNC angiotensin aldosterone system (RAAS) inhibitors. ACE2 HGNC+ expression signatures were defined by differential expression analysis and characterized by Bayesian integrative analysis of a large compendium of public -omics datasets, resulting in the identification of network modules induced in ACE2 HGNC positive PTEC in DKD MESHD and BK virus nephropathy MESHD. These ACE2 HGNC upregulated cell programs were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing and overlapped significantly with the cellular responses induced by SARS-CoV-2 infection MESHD. Similar cellular programs were activated in ACE2 HGNC-positive PTEC isolated in a urine sample from a COVID19 MESHD patient with acute kidney injury MESHD, suggesting a consistent ACE2 HGNC-coregulated expression program that may interact with SARS-Cov-2 infection MESHD processes. The SARS-CoV-2 receptor associated gene signatures could seed further research into therapeutic strategies for COVID-19 MESHD. Functional networks of gene expression signatures are available for further exploration to researchers at HumanBase (hb.flatironinstitute.org/covid-kidney).

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MeSH Disease
HGNC Genes
Transmission
Seroprevalence


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