Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles
Alcoholic liver disease (ALD) is a leading cause of cirrhosis in the United States, which is characterized by extensive deposition of extracellular matrix proteins and formation of a fibrous scar. Hepatic stellate cells (HSCs) are the major source of collagen type 1 producing myofibroblasts in ALD f...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2020-04-01
|
| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1483 |
| _version_ | 1797934944319700992 |
|---|---|
| author | Xiao Liu Sara Brin Rosenthal Nairika Meshgin Jacopo Baglieri Sami G. Musallam Karin Diggle Kevin Lam Raymond Wu Stephanie Q. Pan Yibu Chen Ken Dorko Sharon Presnell Chris Benner Mojgan Hosseini Hidekazu Tsukamoto David Brenner Tatiana Kisseleva |
| author_facet | Xiao Liu Sara Brin Rosenthal Nairika Meshgin Jacopo Baglieri Sami G. Musallam Karin Diggle Kevin Lam Raymond Wu Stephanie Q. Pan Yibu Chen Ken Dorko Sharon Presnell Chris Benner Mojgan Hosseini Hidekazu Tsukamoto David Brenner Tatiana Kisseleva |
| author_sort | Xiao Liu |
| collection | DOAJ |
| description | Alcoholic liver disease (ALD) is a leading cause of cirrhosis in the United States, which is characterized by extensive deposition of extracellular matrix proteins and formation of a fibrous scar. Hepatic stellate cells (HSCs) are the major source of collagen type 1 producing myofibroblasts in ALD fibrosis. However, the mechanism of alcohol‐induced activation of human and mouse HSCs is not fully understood. We compared the gene‐expression profiles of primary cultured human HSCs (hHSCs) isolated from patients with ALD (n = 3) or without underlying liver disease (n = 4) using RNA‐sequencing analysis. Furthermore, the gene‐expression profile of ALD hHSCs was compared with that of alcohol‐activated mHSCs (isolated from intragastric alcohol‐fed mice) or CCl4‐activated mouse HSCs (mHSCs). Comparative transcriptome analysis revealed that ALD hHSCs, in addition to alcohol‐activated and CCl4‐activated mHSCs, share the expression of common HSC activation (Col1a1 [collagen type I alpha 1 chain], Acta1 [actin alpha 1, skeletal muscle], PAI1 [plasminogen activator inhibitor‐1], TIMP1 [tissue inhibitor of metalloproteinase 1], and LOXL2 [lysyl oxidase homolog 2]), indicating that a common mechanism underlies the activation of human and mouse HSCs. Furthermore, alcohol‐activated mHSCs most closely recapitulate the gene‐expression profile of ALD hHSCs. We identified the genes that are similarly and uniquely up‐regulated in primary cultured alcohol‐activated hHSCs and freshly isolated mHSCs, which include CSF1R (macrophage colony‐stimulating factor 1 receptor), PLEK (pleckstrin), LAPTM5 (lysosmal‐associated transmembrane protein 5), CD74 (class I transactivator, the invariant chain), CD53, MMP9 (matrix metallopeptidase 9), CD14, CTSS (cathepsin S), TYROBP (TYRO protein tyrosine kinase‐binding protein), and ITGB2 (integrin beta‐2), and other genes (compared with CCl4‐activated mHSCs). Conclusion: We identified genes in alcohol‐activated mHSCs from intragastric alcohol‐fed mice that are largely consistent with the gene‐expression profile of primary cultured hHSCs from patients with ALD. These genes are unique to alcohol‐induced HSC activation in two species, and therefore may become targets or readout for antifibrotic therapy in experimental models of ALD. |
| first_indexed | 2024-04-10T18:06:48Z |
| format | Article |
| id | doaj.art-1a716209002d475599954c71be02bd75 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T18:06:48Z |
| publishDate | 2020-04-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-1a716209002d475599954c71be02bd752023-02-02T12:41:55ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2020-04-014460662610.1002/hep4.1483Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression ProfilesXiao Liu0Sara Brin Rosenthal1Nairika Meshgin2Jacopo Baglieri3Sami G. Musallam4Karin Diggle5Kevin Lam6Raymond Wu7Stephanie Q. Pan8Yibu Chen9Ken Dorko10Sharon Presnell11Chris Benner12Mojgan Hosseini13Hidekazu Tsukamoto14David Brenner15Tatiana Kisseleva16Department of Surgery University of California, San Diego La Jolla CACenter for Computational Biology & Bioinformatics University of California, San Diego La Jolla CADepartment of Surgery University of California, San Diego La Jolla CADepartment of Surgery University of California, San Diego La Jolla CADepartment of Surgery University of California, San Diego La Jolla CADepartment of Medicine University of California, San Diego La Jolla CADepartment of Medicine University of California, San Diego La Jolla CASouthern California Research Center for ALPD & Cirrhosis Keck School of Medicine of the University of Southern California Los Angeles CASouthern California Research Center for ALPD & Cirrhosis Keck School of Medicine of the University of Southern California Los Angeles CABioinformatics Services Keck School of Medicine of the University of Southern California Los Angeles CASamsara Sciences San Diego CASamsara Sciences San Diego CADepartment of Medicine University of California, San Diego La Jolla CADepartment of Pathology University of California, San Diego La Jolla CASouthern California Research Center for ALPD & Cirrhosis Keck School of Medicine of the University of Southern California Los Angeles CADepartment of Medicine University of California, San Diego La Jolla CADepartment of Surgery University of California, San Diego La Jolla CAAlcoholic liver disease (ALD) is a leading cause of cirrhosis in the United States, which is characterized by extensive deposition of extracellular matrix proteins and formation of a fibrous scar. Hepatic stellate cells (HSCs) are the major source of collagen type 1 producing myofibroblasts in ALD fibrosis. However, the mechanism of alcohol‐induced activation of human and mouse HSCs is not fully understood. We compared the gene‐expression profiles of primary cultured human HSCs (hHSCs) isolated from patients with ALD (n = 3) or without underlying liver disease (n = 4) using RNA‐sequencing analysis. Furthermore, the gene‐expression profile of ALD hHSCs was compared with that of alcohol‐activated mHSCs (isolated from intragastric alcohol‐fed mice) or CCl4‐activated mouse HSCs (mHSCs). Comparative transcriptome analysis revealed that ALD hHSCs, in addition to alcohol‐activated and CCl4‐activated mHSCs, share the expression of common HSC activation (Col1a1 [collagen type I alpha 1 chain], Acta1 [actin alpha 1, skeletal muscle], PAI1 [plasminogen activator inhibitor‐1], TIMP1 [tissue inhibitor of metalloproteinase 1], and LOXL2 [lysyl oxidase homolog 2]), indicating that a common mechanism underlies the activation of human and mouse HSCs. Furthermore, alcohol‐activated mHSCs most closely recapitulate the gene‐expression profile of ALD hHSCs. We identified the genes that are similarly and uniquely up‐regulated in primary cultured alcohol‐activated hHSCs and freshly isolated mHSCs, which include CSF1R (macrophage colony‐stimulating factor 1 receptor), PLEK (pleckstrin), LAPTM5 (lysosmal‐associated transmembrane protein 5), CD74 (class I transactivator, the invariant chain), CD53, MMP9 (matrix metallopeptidase 9), CD14, CTSS (cathepsin S), TYROBP (TYRO protein tyrosine kinase‐binding protein), and ITGB2 (integrin beta‐2), and other genes (compared with CCl4‐activated mHSCs). Conclusion: We identified genes in alcohol‐activated mHSCs from intragastric alcohol‐fed mice that are largely consistent with the gene‐expression profile of primary cultured hHSCs from patients with ALD. These genes are unique to alcohol‐induced HSC activation in two species, and therefore may become targets or readout for antifibrotic therapy in experimental models of ALD.https://doi.org/10.1002/hep4.1483 |
| spellingShingle | Xiao Liu Sara Brin Rosenthal Nairika Meshgin Jacopo Baglieri Sami G. Musallam Karin Diggle Kevin Lam Raymond Wu Stephanie Q. Pan Yibu Chen Ken Dorko Sharon Presnell Chris Benner Mojgan Hosseini Hidekazu Tsukamoto David Brenner Tatiana Kisseleva Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles Hepatology Communications |
| title | Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles |
| title_full | Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles |
| title_fullStr | Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles |
| title_full_unstemmed | Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles |
| title_short | Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles |
| title_sort | primary alcohol activated human and mouse hepatic stellate cells share similarities in gene expression profiles |
| url | https://doi.org/10.1002/hep4.1483 |
| work_keys_str_mv | AT xiaoliu primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT sarabrinrosenthal primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT nairikameshgin primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT jacopobaglieri primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT samigmusallam primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT karindiggle primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT kevinlam primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT raymondwu primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT stephanieqpan primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT yibuchen primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT kendorko primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT sharonpresnell primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT chrisbenner primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT mojganhosseini primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT hidekazutsukamoto primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT davidbrenner primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles AT tatianakisseleva primaryalcoholactivatedhumanandmousehepaticstellatecellssharesimilaritiesingeneexpressionprofiles |