Extracellular vesicles derived from fat-laden hepatocytes undergoing chemical hypoxia promote a pro-fibrotic phenotype in hepatic stellate cells

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Alejandra HernándezHan Moshage

Abstract

The transition from steatosis to non-alcoholic steatohepatitis (NASH) is a key issue in non-alcoholic fatty liver disease (NAFLD). Observations in patients with obstructive sleep apnea syndrome (OSAS) suggest that hypoxia contributes to progression to NASH and liver fibrosis, and the release of extracellular vesicles (EVs) by injured hepatocytes has been implicated in NAFLD progression. To evaluate the effects of hypoxia on hepatic pro-fibrotic response and EV release in experimental NAFLD and to assess cellular crosstalk between hepatocytes and human hepatic stellate cells (LX-2). HepG2 cells were treated with fatty acids and subjected to chemically induced hypoxia using the hypoxia-inducible factor 1 alpha (HIF-1α) stabilizer cobalt chloride (CoCl2). Lipid droplets, oxidative stress, apoptosis and pro-inflammatory and pro-fibrotic-associated genes were assessed. EVs were isolated by ultracentrifugation. LX-2 cells were treated with EVs from hepatocytes. The CDAA-fed mouse model was used to assess the effects of intermittent hypoxia (IH) in experimental NASH. Chemical hypoxia increased steatosis, oxidative stress, apoptosis and pro-inflammatory and pro-fibrotic gene expressions in fat-laden HepG2 cells. Chemical hypoxia also i...Continue Reading

Citations

Sep 26, 2020·Frontiers in Medicine·Francisco IdalsoagaJuan Pablo Arab
Nov 12, 2020·International Journal of Molecular Sciences·Julio Plaza-DíazAna I Álvarez-Mercado
Nov 5, 2020·Biomolecules·Vicneswarry DorairajNor Azian Abdul Murad
Jan 21, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Alexandre VillardRamaroson Andriantsitohaina
May 3, 2021·Journal of Translational Medicine·Jingyao CaiZeng Ling
May 11, 2021·World Journal of Gastroenterology : WJG·Isabela Macedo Lopes Vasques-Monteiro, Vanessa Souza-Mello
Aug 8, 2021·Cells·Beatrice FogliaMaurizio Parola

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