TY - JOUR
T1 - Extracellular vesicles derived from liver sinusoidal endothelial cells inhibit the activation of hepatic stellate cells and kupffer cells in vitro
AU - Wang, Junyu
AU - Wu, Zongmei
AU - Xia, Mengmeng
AU - Serna, Sandra
AU - Arroyave Ospina, Johanna Carolina
AU - Buist-Homan, Manon
AU - Harmsen, Marco
AU - Moshage, Han J.
PY - 2023/12
Y1 - 2023/12
N2 - Background: Liver sinusoidal endothelial cells (LSECs) play a crucial role in maintaining liver microcirculation and homeostasis. In chronic liver diseases, hepatic stellate cells (HSCs) and Kupffer cells (KCs) become activated and LSECs undergo dedifferentiation and capillarization, hampering their normal function. Although KCs and HSCs are intimately involved in the onset and progression of inflammation and fibrosis in chronic liver disease, the role of LSECs in the development of chronic liver diseases remains unclear. Extracellular vesicles (EVs) are released from a variety of cells and contain a plethora of bioactive molecules, including proteins and RNAs and are important mediators of intercellular communication. Aim: to investigate the effect of LSEC-derived EVs on the activation of KCs and HSCs. Methods: Primary rat LSECs, HSCs and KCs were isolated from male Wistar rats. EVs were isolated from condition medium (CM) of LSECs by ultracentrifugation and evaluated by nanoparticle tracking analysis, transmission electron microscopy and determination of specific markers. EVs were added to target cells for 24/72 hours. Gene expression was determined by qPCR and protein expression was determined by Western blot and immunofluorescence and proliferation of cells by Xcelligence and BrdU assay. Results: LSECs-derived EVs reduced the expression of the fibrotic markers collagen type 1 and α-smooth muscle actin (αSMA) in activated HSCs. LSECs-derived EVs significantly suppressed proliferation of activated HSCs. EVs also decreased the expression of inflammatory genes in activated KCs in vitro: iNOS by 72.6%, TNF-α by 54.9%, IL-6 by 35.6%, and IL-1β by 59.5%. Conclusion: EVs released from normal LSECs inhibit the activation of HSCs and the inflammatory phenotype of KCs. LSECs are therefore crucial in maintaining normal liver homeostasis. Elucidating the content of these EVs may lead to the identification of novel therapeutic and/or diagnostic targets for chronic liver diseases.
AB - Background: Liver sinusoidal endothelial cells (LSECs) play a crucial role in maintaining liver microcirculation and homeostasis. In chronic liver diseases, hepatic stellate cells (HSCs) and Kupffer cells (KCs) become activated and LSECs undergo dedifferentiation and capillarization, hampering their normal function. Although KCs and HSCs are intimately involved in the onset and progression of inflammation and fibrosis in chronic liver disease, the role of LSECs in the development of chronic liver diseases remains unclear. Extracellular vesicles (EVs) are released from a variety of cells and contain a plethora of bioactive molecules, including proteins and RNAs and are important mediators of intercellular communication. Aim: to investigate the effect of LSEC-derived EVs on the activation of KCs and HSCs. Methods: Primary rat LSECs, HSCs and KCs were isolated from male Wistar rats. EVs were isolated from condition medium (CM) of LSECs by ultracentrifugation and evaluated by nanoparticle tracking analysis, transmission electron microscopy and determination of specific markers. EVs were added to target cells for 24/72 hours. Gene expression was determined by qPCR and protein expression was determined by Western blot and immunofluorescence and proliferation of cells by Xcelligence and BrdU assay. Results: LSECs-derived EVs reduced the expression of the fibrotic markers collagen type 1 and α-smooth muscle actin (αSMA) in activated HSCs. LSECs-derived EVs significantly suppressed proliferation of activated HSCs. EVs also decreased the expression of inflammatory genes in activated KCs in vitro: iNOS by 72.6%, TNF-α by 54.9%, IL-6 by 35.6%, and IL-1β by 59.5%. Conclusion: EVs released from normal LSECs inhibit the activation of HSCs and the inflammatory phenotype of KCs. LSECs are therefore crucial in maintaining normal liver homeostasis. Elucidating the content of these EVs may lead to the identification of novel therapeutic and/or diagnostic targets for chronic liver diseases.
M3 - Meeting Abstract
SN - 0270-9139
JO - Hepatology
JF - Hepatology
ER -