This article is a Preprint
Preprints are preliminary research reports that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Preprints posted online allow authors to receive rapid feedback and the entire scientific community can appraise the work for themselves and respond appropriately. Those comments are posted alongside the preprints for anyone to read them and serve as a post publication assessment.
SARS-CoV-2 Spike Protein Receptor Binding-ACE2 Interaction Increases Carbohydrate Sulfotransferases and Reduces N-Acetylgalactosamine-4-Sulfatase through Phospho-p38-MAPK and RB-E2F1 (preprint)
medrxiv; 2023.
Preprint
in English
| medRxiv | ID: ppzbmed-10.1101.2023.01.24.23284890
ABSTRACT
Immunostaining in lungs of patients who died with Covid-19 infection showed increased intensity and distribution of chondroitin sulfate and carbohydrate sulfotransferase (CHST)15 and decline in N-acetylgalactostamine-4-sulfatase (Arylsulfatase B; ARSB). To explain these findings, human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain (SPRBD) and transcriptional mechanisms investigated. Phospho-p38 MAPK and phospho-Smad3 increased following exposure to the SPRBD, and their inhibition suppressed CHST15 and CHST11 promoter activation. Decline in ARSB was mediated by phospho-38 MAPK-induced N-terminal Rb phosphorylation and the associated decline in E2F1 binding to the ARSB promoter. The increases in chondroitin sulfotransferases were inhibited by the p38-MAPK inhibitor SB203580 and by the Smad3 inhibitor SIS3 and by treatment with the antihistamine desloratadine and the antibiotic monensin. Since accumulation of chondroitin sulfates is associated with fibrotic lung conditions and diffuse alveolar damage, increased attention to p38-MAPK inhibitors may be beneficial in Covid-19 infection.
Full text:
Available
Collection:
Preprints
Database:
medRxiv
Main subject:
Adenocarcinoma, Bronchiolo-Alveolar
/
Severe Acute Respiratory Syndrome
/
COVID-19
/
Lung Diseases
Language:
English
Year:
2023
Document Type:
Preprint
Similar
MEDLINE
...
LILACS
LIS