Elevated Autotaxin and LPA Levels during Chronic Viral Hepatitis and Hepatocellular Carcinoma Associate with Systemic Immune Activation

Kostadinova, Lenche; Shive, Carey L.; Anthony, Donald D.

doi:10.3390/cancers11121867

Cited by 15 publications

(10 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that HCV, HIV and HBV viral increase Enpp2 mRNA expression in infected cells and/or to raise systemic ATX levels (42)(43)(44). As shown here, increased ENPP2 mRNA expression was detected in nasopharyngeal swab samples from COVID-19 patients in comparison to non-infected healthy controls (Fig.…”

Section: Discussionsupporting

confidence: 75%

Increased Autotaxin levels in severe COVID-19, correlating with IL-6 levels, endothelial dysfunction biomarkers, and impaired functions of dendritic cells

Nikitopoulou

Fanidis

Ntatsoulis

et al. 2021

Preprint

View full text Add to dashboard Cite

Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalysing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signalling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signalling 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 RNAseq datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, that exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, worth of suggesting that its pharmacological targeting might represent an additional therapeutic option.

show abstract

Section: Discussionsupporting

confidence: 75%

Increased Autotaxin levels in severe COVID-19, correlating with IL-6 levels, endothelial dysfunction biomarkers, and impaired functions of dendritic cells

Nikitopoulou

Fanidis

Ntatsoulis

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that HCV, HIV, and HBV viruses increase Enpp2 mRNA expression in infected cells and/or raise systemic ATX levels [ 27 , 44 , 45 ]. As shown here, increased ENPP2 mRNA expression was detected in nasopharyngeal swab samples from COVID-19 patients in comparison to non-infected healthy controls ( Figure 1 ), while scRNAseq re-analysis revealed that the highest ENPP2 expressing cells in swabs are immune cells ( Figure 5 A and Figure S5A ), suggesting that CoV-2 infection stimulates ENPP2 expression from immune cells in the nasopharynx.…”

Section: Discussionmentioning

confidence: 99%

Increased Autotaxin Levels in Severe COVID-19, Correlating with IL-6 Levels, Endothelial Dysfunction Biomarkers, and Impaired Functions of Dendritic Cells

Nikitopoulou

Fanidis

Ntatsoulis

et al. 2021

IJMS

View full text Add to dashboard Cite

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.

show abstract

“…Viral infections have been shown to increase systemic ATX levels, including HCV, HIV and HBV ( 43 , 58 , 59 ), while LPA has been also shown to directly affect HCV viral infection and replication ( 43 , 60 ). Increased ENPP2 mRNA expression was detected in nasopharyngeal swabs from COVID-19 patients, likely from immune cells ( 61 ), suggesting that ATX/LPA might stimulate viral infections, that could include SARS-CoV-2.…”

Section: Autotaxin (Atx; Enpp2 ) and Covid-19mentioning

confidence: 99%

Commonalities Between ARDS, Pulmonary Fibrosis and COVID-19: The Potential of Autotaxin as a Therapeutic Target

et al. 2021

View full text Add to dashboard Cite

Severe COVID-19 is characterized by acute respiratory distress syndrome (ARDS)-like hyperinflammation and endothelial dysfunction, that can lead to respiratory and multi organ failure and death. Interstitial lung diseases (ILD) and pulmonary fibrosis confer an increased risk for severe disease, while a subset of COVID-19-related ARDS surviving patients will develop a fibroproliferative response that can persist post hospitalization. Autotaxin (ATX) is a secreted lysophospholipase D, largely responsible for the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling lysophospholipid with multiple effects in pulmonary and immune cells. In this review, we discuss the similarities of COVID-19, ARDS and ILDs, and suggest ATX as a possible pathologic link and a potential common therapeutic target.

show abstract

Elevated Autotaxin and LPA Levels during Chronic Viral Hepatitis and Hepatocellular Carcinoma Associate with Systemic Immune Activation

Cited by 15 publications

References 115 publications

Increased Autotaxin levels in severe COVID-19, correlating with IL-6 levels, endothelial dysfunction biomarkers, and impaired functions of dendritic cells

Increased Autotaxin levels in severe COVID-19, correlating with IL-6 levels, endothelial dysfunction biomarkers, and impaired functions of dendritic cells

Increased Autotaxin Levels in Severe COVID-19, Correlating with IL-6 Levels, Endothelial Dysfunction Biomarkers, and Impaired Functions of Dendritic Cells

Commonalities Between ARDS, Pulmonary Fibrosis and COVID-19: The Potential of Autotaxin as a Therapeutic Target

Contact Info

Product

Resources

About