Primary Alcohol‐Activated Human and Mouse Hepatic Stellate Cells Share Similarities in Gene‐Expression Profiles
Autor: | Ken Dorko, Hidekazu Tsukamoto, Tatiana Kisseleva, Jacopo Baglieri, Nairika Meshgin, Stephanie Q. Pan, Christopher Benner, Sharon Presnell, Karin Diggle, Yibu Chen, Kevin Lam, David A. Brenner, Xiao Liu, Raymond Wu, Sara Brin Rosenthal, Sami G. Musallam, Mojgan Hosseini |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0303 health sciences
Hepatology CD74 LOXL2 Chemistry Actin alpha 1 Original Articles MMP9 Molecular biology 3. Good health 03 medical and health sciences Collagen type I alpha 1 0302 clinical medicine Hepatic stellate cell 030211 gastroenterology & hepatology lcsh:Diseases of the digestive system. Gastroenterology Original Article lcsh:RC799-869 030304 developmental biology Cathepsin S TIMP1 |
Zdroj: | Hepatology Communications Hepatology Communications, Vol 4, Iss 4, Pp 606-626 (2020) |
ISSN: | 2471-254X |
Popis: | 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. We identified genes in alcohol‐activated mHSCs from IG 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. |
Databáze: | OpenAIRE |
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