The spike protein of SARS-CoV-2 induces heme oxygenase-1: Pathophysiologic implications.
Biochim Biophys Acta Mol Basis Dis
; 1868(3): 166322, 2022 03 01.
Article
in English
| MEDLINE | ID: covidwho-1637812
ABSTRACT
BACKGROUND:
Acute kidney injury (AKI) is both a consequence and determinant of outcomes in COVID-19. The kidney is one of the major organs infected by the causative virus, SARS-CoV-2. Viral entry into cells requires the viral spike protein, and both the virus and its spike protein appear in the urine of COVID-19 patients with AKI. We examined the effects of transfecting the viral spike protein of SARS-CoV-2 in kidney cell lines.METHODS:
HEK293, HEK293-ACE2+ (stably overexpressing ACE2), and Vero E6 cells having endogenous ACE2 were transfected with SARS-CoV-2 spike or control plasmid. Assessment of gene and protein expression, and syncytia formation was performed, and the effects of quercetin on syncytia formation examined.FINDINGS:
Spike transfection in HEK293-ACE2+ cells caused syncytia formation, cellular sloughing, and focal denudation of the cell monolayer; transfection in Vero E6 cells also caused syncytia formation. Spike expression upregulated potentially nephrotoxic genes (TNF-α, MCP-1, and ICAM1). Spike upregulated the cytoprotective gene HO-1 and relevant signaling pathways (p-Akt, p-STAT3, and p-p38). Quercetin, an HO-1 inducer, reduced syncytia formation and spike protein expression.INTERPRETATION:
The major conclusions of the study are 1) Spike protein expression in kidney cells provides a relevant model for the study of maladaptive and adaptive responses germane to AKI in COVID-19; 2) such spike protein expression upregulates HO-1; and 3) quercetin, an HO-1 inducer, may provide a clinically relevant/feasible protective strategy in AKI occurring in the setting of COVID-19.FUNDING:
R01-DK119167 (KAN), R01-AI100911 (JPG), P30-DK079337; R01-DK059600 (AA).Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Heme Oxygenase-1
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Biochim Biophys Acta Mol Basis Dis
Year:
2022
Document Type:
Article
Affiliation country:
J.bbadis.2021.166322
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