WFRF:(Jung Bongnam)
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HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P(1)) promotes regeneration and suppresses fibrosis in the liver
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- Ding, Bi-Sen (författare)
- 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.
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- Liu, Catherine H. (författare)
- Cornell Univ, Dept Pathol & Lab Med, Ctr Vasc Biol, Weill Cornell Med, New York, NY 10021 USA.
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- Sun, Yue (författare)
- 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.
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- 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. (creator_code:org_t)
- American Society for Clinical Investigation, 2016
- 2016
- Engelska.
- Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 1:21
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
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- Ding, Bi-Sen
- Liu, Catherine H ...
- Sun, Yue
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- Jung, Bongnam
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- Nielsen, Lars Bo
- Schwab, Susan R.
- Rafii, Shahin
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