Format:
20
ISSN:
2211-1247
Content:
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.
Note:
Gesehen am 13.12.2021
In:
Cell reports, Maryland Heights, MO : Cell Press, 2012, 37(2021), 4, Artikel-ID 109897, Seite 1-20, 2211-1247
In:
volume:37
In:
year:2021
In:
number:4
In:
elocationid:109897
In:
pages:1-20
In:
extent:20
Language:
English
DOI:
10.1016/j.celrep.2021.109897
URL:
Volltext
(lizenzpflichtig)
URL:
Volltext
(lizenzpflichtig)
Bookmarklink