Adenosine deaminase 2 produced by infiltrative monocytes promotes liver fibrosis in nonalcoholic fatty liver disease
Elevated circulating activity of adenosine deaminase 2 (ADA2) is associated with liver fibrosis in nonalcoholic fatty liver disease (NAFLD). In the liver of NAFLD patients, ADA2-positive portal macrophages are significantly associated with the degree of liver fibrosis. These liver macrophages are CD...
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| Hauptverfasser: | , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
26 October 2021
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| In: |
Cell reports
Year: 2021, Jahrgang: 37, Heft: 4, Pages: 1-20 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.109897 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2021.109897 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S221112472101367X 
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| Verfasserangaben: | Shilpa Tiwari-Heckler, Eric U. Yee, Yusuf Yalcin, Jiwoon Park, Duc-Huy T. Nguyen, Wenda Gao, Eva Csizmadia, Nezam Afdhal, Kenneth J. Mukamal, Simon C. Robson, Michelle Lai, Robert E. Schwartz, Z. Gordon Jiang |
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| 245 | 1 | 0 | |a Adenosine deaminase 2 produced by infiltrative monocytes promotes liver fibrosis in nonalcoholic fatty liver disease |c Shilpa Tiwari-Heckler, Eric U. Yee, Yusuf Yalcin, Jiwoon Park, Duc-Huy T. Nguyen, Wenda Gao, Eva Csizmadia, Nezam Afdhal, Kenneth J. Mukamal, Simon C. Robson, Michelle Lai, Robert E. Schwartz, Z. Gordon Jiang |
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| 520 | |a Elevated circulating activity of adenosine deaminase 2 (ADA2) is associated with liver fibrosis in nonalcoholic fatty liver disease (NAFLD). In the liver of NAFLD patients, ADA2-positive portal macrophages are significantly associated with the degree of liver fibrosis. These liver macrophages are CD14- and CD16-positive and co-express chemokine receptors CCR2, CCR5, and CXCR3, indicating infiltrative monocyte origin. Human circulatory monocytes release ADA2 upon macrophage differentiation in vitro. When stimulated by recombinant human ADA2 (rhADA2), human monocyte-derived macrophages demonstrate upregulation of pro-inflammatory and pro-fibrotic genes, including PDGF-B, a key pro-fibrotic cytokine. This PDGF-B upregulation is reproduced by inosine, the enzymatic product of ADA2, but not adenosine, and is abolished by E359N, a loss-of-function mutation in ADA2. Finally, rhADA2 also stimulates PDGF-B production from Kupffer cells in primary human liver spheroids. Together, these data suggest that infiltrative monocytes promote fibrogenesis in NAFLD via ADA2-mediated autocrine/paracrine signaling culminating in enhanced PDGF-B production. | ||
| 650 | 4 | |a adenosine deaminase 2 | |
| 650 | 4 | |a cat eye syndrome chromosome region 1 | |
| 650 | 4 | |a Kupffer cells | |
| 650 | 4 | |a liver fibrosis | |
| 650 | 4 | |a Nonalcoholic fatty liver disease | |
| 650 | 4 | |a nonalcoholic steatohepatitis | |
| 650 | 4 | |a platelet derived growth factor B | |
| 650 | 4 | |a portal macrophages | |
| 700 | 1 | |a Yee, Eric U. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yalcin, Yusuf |e VerfasserIn |4 aut | |
| 700 | 1 | |a Park, Jiwoon |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nguyen, Duc-Huy T. |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Schwartz, Robert E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jiang, Z. Gordon |e VerfasserIn |4 aut | |
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