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Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol

Authors :
Moses New-Aaron
Siva Sankar Koganti
Murali Ganesan
Sharma Kanika
Vikas Kumar
Weimin Wang
Edward Makarov
Kusum K. Kharbanda
Larisa Y. Poluektova
Natalia A. Osna
Source :
International Journal of Molecular Sciences, Vol 24, Iss 6, p 5346 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Liver disease is one of the leading comorbidities in HIV infection. The risk of liver fibrosis development is potentiated by alcohol abuse. In our previous studies, we reported that hepatocytes exposed to HIV and acetaldehyde undergo significant apoptosis, and the engulfment of apoptotic bodies (ABs) by hepatic stellate cells (HSC) potentiates their pro-fibrotic activation. However, in addition to hepatocytes, under the same conditions, ABs can be generated from liver-infiltrating immune cells. The goal of this study is to explore whether lymphocyte-derived ABs trigger HSC profibrotic activation as strongly as hepatocyte-derived ABs. ABs were generated from Huh7.5-CYP2E1 (RLW) cells and Jurkat cells treated with HIV+acetaldehyde and co-culture with HSC to induce their pro-fibrotic activation. ABs cargo was analyzed by proteomics. ABs generated from RLW, but not from Jurkat cells activated fibrogenic genes in HSC. This was driven by the expression of hepatocyte-specific proteins in ABs cargo. One of these proteins is Hepatocyte-Derived Growth Factor, for which suppression attenuates pro-fibrotic activation of HSC. In mice humanized with only immune cells but not human hepatocytes, infected with HIV and fed ethanol, liver fibrosis was not observed. We conclude that HIV+ABs of hepatocyte origin promote HSC activation, which potentially may lead to liver fibrosis progression.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
24
Issue :
6
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.6c285c24e80e4a9199f05390a451df3a
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms24065346