Increased Autotaxin Levels in Severe COVID-19, Correlating with IL-6 Levels, Endothelial Dysfunction Biomarkers, and Impaired Functions of Dendritic Cells.
Int J Mol Sci
; 22(18)2021 Sep 16.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1409704
Preprint
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Este artículo de revista científica es probablemente basado en un preprint previamente disponible, por medio del reconocimiento de similitud realizado por una máquina. La confirmación humana aún está pendiente.
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ABSTRACT
Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signaling in pulmonary injury, inflammation, and fibrosis. Here, increased ENPP2 mRNA levels were detected in immune cells from nasopharyngeal swab samples of COVID-19 patients, and increased ATX serum levels were found in severe COVID-19 patients. ATX serum levels correlated with the corresponding increased serum levels of IL-6 and endothelial damage biomarkers, suggesting an interplay of the ATX/LPA axis with hyperinflammation and the associated vascular dysfunction in COVID-19. Accordingly, dexamethasone (Dex) treatment of mechanically ventilated patients reduced ATX levels, as shown in two independent cohorts, indicating that the therapeutic benefits of Dex include the suppression of ATX. Moreover, large scale analysis of multiple single cell RNA sequencing datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, which exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, suggesting that its pharmacological targeting might represent an additional therapeutic option, both during and after hospitalization.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Fosfodiesterasa
/
Células Dendríticas
/
Hidrolasas Diéster Fosfóricas
/
SARS-CoV-2
/
COVID-19
Tipo de estudio:
Estudio de cohorte
/
Estudios diagnósticos
/
Estudio observacional
/
Estudio pronóstico
Límite:
Adulto
/
Anciano
/
Femenino
/
Humanos
/
Masculino
/
Middle aged
Idioma:
Inglés
Año:
2021
Tipo del documento:
Artículo
País de afiliación:
Ijms221810006
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