Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol
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...
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2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5346 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Moses New-Aaron |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:26:06Z |
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| id | doaj.art-6c285c24e80e4a9199f05390a451df3a |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:06Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6c285c24e80e4a9199f05390a451df3a2023-11-17T11:32:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246534610.3390/ijms24065346Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and EthanolMoses New-Aaron0Siva Sankar Koganti1Murali Ganesan2Sharma Kanika3Vikas Kumar4Weimin Wang5Edward Makarov6Kusum K. Kharbanda7Larisa Y. Poluektova8Natalia A. Osna9Department of Environmental Health, Occupational Health and Toxicology, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USADepartment of Genetics Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68105, USADepartment of Genetics Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68105, USADepartment of Genetics Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68105, USADepartment of Genetics Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68105, USAResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68105, USADepartment of Environmental Health, Occupational Health and Toxicology, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USALiver 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.https://www.mdpi.com/1422-0067/24/6/5346apoptotic bodiesHIValcoholhepatic stellate cellsHDGFliver fibrosis |
| spellingShingle | 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 Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol International Journal of Molecular Sciences apoptotic bodies HIV alcohol hepatic stellate cells HDGF liver fibrosis |
| title | Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol |
| title_full | Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol |
| title_fullStr | Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol |
| title_full_unstemmed | Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol |
| title_short | Hepatocyte-Specific Triggering of Hepatic Stellate Cell Profibrotic Activation by Apoptotic Bodies: The Role of Hepatoma-Derived Growth Factor, HIV, and Ethanol |
| title_sort | hepatocyte specific triggering of hepatic stellate cell profibrotic activation by apoptotic bodies the role of hepatoma derived growth factor hiv and ethanol |
| topic | apoptotic bodies HIV alcohol hepatic stellate cells HDGF liver fibrosis |
| url | https://www.mdpi.com/1422-0067/24/6/5346 |
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