GDF11 induces mild hepatic fibrosis independent of metabolic health
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F20%3A00073487" target="_blank" >RIV/00159816:_____/20:00073487 - isvavai.cz</a>
Result on the web
<a href="https://www.aging-us.com/article/104182/text" target="_blank" >https://www.aging-us.com/article/104182/text</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.18632/aging.104182" target="_blank" >10.18632/aging.104182</a>
Alternative languages
Result language
angličtina
Original language name
GDF11 induces mild hepatic fibrosis independent of metabolic health
Original language description
Background & aims: Growth Differentiation Factor 11 (GDF11) is an anti-aging factor, yet its role in liver diseases is not established. We evaluated the role of GDF11 in healthy conditions and in the transition from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Results: GDF11 mRNA levels positively correlated with NAFLD activity score and with CPT1, SREBP, PPAR gamma and Col1A1 mRNA levels, and associated to portal fibrosis, in morbidly obese patients with NAFLD/NASH. GDF11-treatedmice showed mildly exacerbated hepatic collagen deposition, accompanied by weight loss and without changes in liver steatosis or inflammation. GDF11 triggered ALK5-dependent SMAD2/3 nuclear translocation and the pro-fibrogenic activation of HSC. Conclusions: GDF11 supplementation promotes mild liver fibrosis. Even considering its beneficial metabolic effects, caution should be taken when considering therapeutics that regulate GDF11. Methods: We analyzed liver biopsies from a cohort of 33 morbidly obese adults with NAFLD/NASH. We determined the correlations in mRNA expression levels between GDF11 and genes involved in NAFLD-to-NASH progression and with pathological features. We also exposed wild type or obese mice with NAFLD to recombinant GDF11 by daily intra-peritoneal injection and monitor the hepatic pathological changes. Finally, we analyzed GDF11-activated signaling pathways in hepatic stellate cells (HSC).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
<a href="/en/project/EF15_003%2F0000492" target="_blank" >EF15_003/0000492: Unveiling the molecular determinants of agingto design new therapeutics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Aging-US
ISSN
1945-4589
e-ISSN
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Volume of the periodical
12
Issue of the periodical within the volume
20
Country of publishing house
US - UNITED STATES
Number of pages
23
Pages from-to
20024-20046
UT code for WoS article
000583838700016
EID of the result in the Scopus database
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