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Stiffness-induced modulation of ERG transcription factor in chronic liver disease

by Nulan, Yeldos , Ștefănescu, Horia , Berzigotti, Annalisa , Felli, Eric , Wang, Cong , Lozano, Juan José , Guixé-Muntet, Sergi , Bosch, Jaime , Gracia-Sancho, Jordi , Selicean, Sonia-Emilia

in Angiogenesis / Datasets / Experiments / Genes / Hypertension / Inflammation / Liver cirrhosis / Liver diseases / Localization / Proteins / Transcription factors

2024

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Stiffness-induced modulation of ERG transcription factor in chronic liver disease

by Nulan, Yeldos , Ștefănescu, Horia , Berzigotti, Annalisa , Felli, Eric , Wang, Cong , Lozano, Juan José , Guixé-Muntet, Sergi , Bosch, Jaime , Gracia-Sancho, Jordi , Selicean, Sonia-Emilia

in Angiogenesis / Datasets / Experiments / Genes / Hypertension / Inflammation / Liver cirrhosis / Liver diseases / Localization / Proteins / Transcription factors

2024

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Stiffness-induced modulation of ERG transcription factor in chronic liver disease

by Nulan, Yeldos , Ștefănescu, Horia , Berzigotti, Annalisa , Felli, Eric , Wang, Cong , Lozano, Juan José , Guixé-Muntet, Sergi , Bosch, Jaime , Gracia-Sancho, Jordi , Selicean, Sonia-Emilia

in Angiogenesis / Datasets / Experiments / Genes / Hypertension / Inflammation / Liver cirrhosis / Liver diseases / Localization / Proteins / Transcription factors

2024

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Journal Article

Stiffness-induced modulation of ERG transcription factor in chronic liver disease

Nulan, Yeldos,

Ștefănescu, Horia,

Berzigotti, Annalisa,

Felli, Eric,

Wang, Cong,

Lozano, Juan José,

Guixé-Muntet, Sergi,

Bosch, Jaime,

Gracia-Sancho, Jordi,

Selicean, Sonia-Emilia

2024

Overview

Chronic liver disease (CLD) is characterised by liver sinusoidal endothelial cells (LSECs) dysfunction. Mechanical forces and inflammation are among the leading factors. ETS-related gene (ERG) is an endothelial-specific transcription factor, involved in maintaining cell quiescence and homeostasis. Our study aimed to understand the expression and modulation of ERG in CLD. ERG expression was characterised and correlated to clinical data in human liver cirrhosis at different disease stages. ERG dynamics in response to stiffness and inflammation were investigated in primary healthy and cirrhotic rat LSEC and in human umbilical vein endothelial cells (HUVECs). ERG is markedly downregulated in cirrhosis independently of disease stage or aetiology and its expression is modulated by substrate stiffness in ECs. Inflammation downregulates ERG in cells on physiological stiffness, but not on high stiffness, suggesting a complementary role of inflammation and stiffness in suppressing ERG. This study outlines ERG as an LSEC inflammation and stiffness-responsive transcription factor in cirrhosis.

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Publisher

Nature Publishing Group

Subject

/ Genes