Galectin-9 protein expression in endothelial cells is positively regulated by histone deacetylase 3.
Galectin-9 expression in endothelial cells can be induced in response to inflammation. However, the mechanism of its expression remains unclear. In this study, we found that interferon-γ (IFN-γ) induced galectin-9 expression in human endothelial cells in a time-dependent manner, which coincided with the activation of histone deacetylase (HDAC). When endothelial cells were treated with the HDAC3 inhibitor, apicidin, or shRNA-HDAC3 knockdown, IFN-γ-induced galectin-9 expression was abolished. Overexpression of HDAC3 induced the interaction between phosphoinositol 3-kinase (PI3K) and IFN response factor 3 (IRF3), leading to IRF3 phosphorylation, nuclear translocation, and galectin-9 expression. HDAC3 functioned as a scaffold protein for PI3K/IRF3 interaction. In addition to galectin-9 expression, IFN-γ also induced galectin-9 location onto plasma membrane, which was HDAC3-independent. Importantly, HDAC3 was essential for the constitutive transcription of PI3K and IRF3, which might be responsible for the basal level of galectin-9 expression. The phosphorylation of IRF3 was essential for galectin-9 expression. This study provides new evidence that HDAC3 regulates galectin-9 expression in endothelial cells via interaction with PI3K-IRF3 signal pathway.
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom.
Saydul
S
Alam
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom.
Hongling
H
Li
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom.
Andriana
A
Margariti
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom.
Daniel
D
Martin
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom.
Anna
A
Zampetaki
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom.
Ouassila
O
Habi
Department of Cardiovascular Science, St. George's University of London, London SW17 0RE, United Kingdom.
Gillian
G
Cockerill
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom.
Yanhua
Y
Hu
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom.
Qingbo
Q
Xu
Cardiovascular Division, King's College London British Heart Founcation Centre, London SE5 9NU, United Kingdom. Electronic address: lingfang.zeng@kcl.ac.uk.
Lingfang
L
Zeng
D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D000099186:Histone Deacetylase 3
D037161:Galectins; D006655:Histone Deacetylases; D050838:Interferon Regulatory Factor-3; D007371:Interferon-gamma; D007372:Interferons; D019869:Phosphatidylinositol 3-Kinases; D000099186:Histone Deacetylase 3; C105032:LGALS9 protein, human