uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P(1)) promotes regeneration and suppresses fibrosis in the liver
Sichuan Univ, Key Lab Birth Defects & Related Dis Women & Child, State Key Lab Biotherapy, Minist Educ,West China Univ Hosp 2, Chengdu, Peoples R China.;Collaborat Innovat Ctr Biotherapy, Chengdu, Peoples R China.;Weill Cornell Med, Ansary Stem Cell Inst, Div Regenerat Med, Dept Med, New York, NY USA..
Cornell Univ, Dept Pathol & Lab Med, Ctr Vasc Biol, Weill Cornell Med, New York, NY 10021 USA..
Sichuan Univ, Key Lab Birth Defects & Related Dis Women & Child, State Key Lab Biotherapy, Minist Educ,West China Univ Hosp 2, Chengdu, Peoples R China.;Collaborat Innovat Ctr Biotherapy, Chengdu, Peoples R China..
Sichuan Univ, Key Lab Birth Defects & Related Dis Women & Child, State Key Lab Biotherapy, Minist Educ,West China Univ Hosp 2, Chengdu, Peoples R China.;Collaborat Innovat Ctr Biotherapy, Chengdu, Peoples R China..
Show others and affiliations
2016 (English)In: JCI Insight, ISSN 2379-3708, Vol. 1, no 21, e87058Article in journal (Refereed) Published
Abstract [en]

Regeneration of hepatic sinusoidal vasculature is essential for non-fibrotic liver regrowth and restoration of its metabolic capacity. However, little is known about how this specialized vascular niche is regenerated. Here we show that activation of endothelial sphingosine-1-phosphate receptor-1 (S1P 1) by its natural ligand bound to HDL (HDL-S1P) induces liver regeneration and curtails fibrosis. In mice lacking HDL-S1P, liver regeneration after partial hepatectomy was impeded and associated with aberrant vascular remodeling, thrombosis and peri-sinusoidal fibrosis. Notably, this "maladaptive repair" phenotype was recapitulated in mice that lack S1P 1 in the endothelium. Reciprocally, enhanced plasma levels of HDL-S1P or administration of SEW2871, a pharmacological agonist specific for S1P 1 enhanced regeneration of metabolically functional vasculature and alleviated fibrosis in mouse chronic injury and cholestasis models. This study shows that natural and pharmacological ligands modulate endothelial S1P 1 to stimulate liver regeneration and inhibit fibrosis, suggesting that activation of this pathway may be a novel therapeutic strategy for liver fibrosis.

Place, publisher, year, edition, pages
2016. Vol. 1, no 21, e87058
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-316427DOI: 10.1172/jci.insight.87058ISI: 000392963700002PubMedID: 28018969OAI: oai:DiVA.org:uu-316427DiVA: diva2:1077937
Funder
NIH (National Institute of Health), R01AI085166
Note

C.H. Liu, Y. Sun, and Y. Chen contributed equally to this work.

Available from: 2017-03-01 Created: 2017-03-01 Last updated: 2017-03-01Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Jung, Bongnam
By organisation
Vascular Biology
Cardiac and Cardiovascular Systems

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 143 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf