Liver fibrosis is a reversible wound-healing response to injury reflecting the critical balance between liver repair and scar formation. Chronic damage leads to progressive substitution of liver parenchyma by scar tissue and ultimately results in liver cirrhosis. Stromal cells (hepatic stellate cells [HSC] and endothelial cells) have been proposed to control the balance between liver fibrosis and regeneration. Here, we show that endosialin, a C-type lectin, expressed in the liver exclusively by HSC and portal fibroblasts, is upregulated in liver fibrosis in mouse and man. Chronic chemically induced liver damage resulted in reduced fibrosis and enhanced hepatocyte proliferation in endosialin-deficient (EN(KO)) mice. Correspondingly, acute-liver-damage-induced hepatocyte proliferation (partial hepatectomy) was increased in EN(KO) mice. A candidate-based screen of known regulators of hepatocyte proliferation identified insulin-like growth factor 2 (IGF2) as selectively endosialin-dependent hepatocyte mitogen. Collectively, the study establishes a critical role of HSC in the reciprocal regulation of fibrogenesis vs. hepatocyte proliferation and identifies endosialin as a therapeutic target in non-neoplastic settings.
Pharmacology, Toxicology and Pharmaceutical Science
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2%
Linguistics
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Other
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Unknown
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24%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 35. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 January 2022.
All research outputs
#1,433,874
of 33,973,571 outputs
Outputs from EMBO Molecular Medicine
#305
of 2,034 outputs
Outputs of similar age
#16,798
of 418,586 outputs
Outputs of similar age from EMBO Molecular Medicine
#8
of 40 outputs
Altmetric has tracked 33,973,571 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,034 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.9. This one has done well, scoring higher than 84% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 418,586 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 40 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
