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@ARTICLE{Sugimoto:299785,
author = {A. Sugimoto and Y. Saito and G. Wang$^*$ and Q. Sun and C.
Yin and K. H. Lee$^*$ and Y. Geng and P. Rajbhandari and C.
Hernandez and M. Steffani and J. Qie and T. Savage and D. M.
Goyal and K. C. Ray and T. V. Neelakantan and D. Yin and J.
Melms and B. M. Lehrich and T. M. Yasaka and S. Liu and M.
Oertel and T. Lan and A. Guillot and M. Peiseler and A.
Filliol and H. Kanzaki and N. Fujiwara and S. Ravi and B.
Izar and M. Brosch and J. Hampe and H. Remotti and J. Argemi
and Z. Sun and T. J. Kendall and Y. Hoshida and F. Tacke and
J. A. Fallowfield and S. K. Blockley-Powell and R. A.
Haeusler and J. B. Steinman and U. B. Pajvani and S. P.
Monga and R. Bataller and M. Masoodi and N. Arpaia and Y. A.
Lee and B. R. Stockwell and H. Augustin$^*$ and R. F.
Schwabe},
title = {{H}epatic stellate cells control liver zonation, size and
functions via {R}-spondin 3.},
journal = {Nature},
volume = {640},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2025-00540},
pages = {752–761},
year = {2025},
note = {#EA:A190# / 640, pages 752–761 (2025)},
abstract = {Hepatic stellate cells (HSCs) have a central pathogenetic
role in the development of liver fibrosis. However, their
fibrosis-independent and homeostatic functions remain poorly
understood1-5. Here we demonstrate that genetic depletion of
HSCs changes WNT activity and zonation of hepatocytes,
leading to marked alterations in liver regeneration,
cytochrome P450 metabolism and injury. We identify R-spondin
3 (RSPO3), an HSC-enriched modulator of WNT signalling, as
responsible for these hepatocyte-regulatory effects of HSCs.
HSC-selective deletion of Rspo3 phenocopies the effects of
HSC depletion on hepatocyte gene expression, zonation, liver
size, regeneration and cytochrome P450-mediated
detoxification, and exacerbates alcohol-associated and
metabolic dysfunction-associated steatotic liver disease.
RSPO3 expression decreases with HSC activation and is
inversely associated with outcomes in patients with
alcohol-associated and metabolic dysfunction-associated
steatotic liver disease. These protective and
hepatocyte-regulating functions of HSCs via RSPO3 resemble
the R-spondin-expressing stromal niche in other organs and
should be integrated into current therapeutic concepts.},
cin = {A190},
ddc = {500},
cid = {I:(DE-He78)A190-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40074890},
doi = {10.1038/s41586-025-08677-w},
url = {https://inrepo02.dkfz.de/record/299785},
}