Sphingosine-1-phosphate promotes liver fibrosis in metabolic dysfunction-associated steatohepatitis

被引：5

作者：

Osawa, Yosuke ^{[1
,2
]}

Kawai, Hironari ^{[2
,3
]}

Nakashima, Keigo ^{[3
,4
]}

Nakaseko, Yuichi ^{[3
,4
]}

Suto, Daisuke ^{[1
]}

Yanagida, Keisuke ^{[5
]}

Hashidate-Yoshida, Tomomi ^{[5
]}

Mori, Taizo ^{[2
]}

Yoshio, Sachiyo ^{[2
]}

Ohtake, Takaaki ^{[1
]}

Shindou, Hideo ^{[5
,6
]}

Kanto, Tatsuya ^{[2
]}

机构：

[1] Int Univ Hlth & Welf Hosp, Dept Gastroenterol, Tochigi, Japan

[2] Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol, Dept Liver Dis, Chiba, Japan

[3] Jikei Univ, Sch Med, Dept Surg, Tokyo, Japan

[4] Int Univ Hlth & Welf Hosp, Dept Surg, Tochigi, Japan

[5] Natl Ctr Global Hlth & Med, Dept Lipid Life Sci, Tokyo, Japan

[6] Univ Tokyo, Dept Med Lipid Sci, Grad Scholl Med, Tokyo, Japan

来源：

PLOS ONE | 2024年 / 19卷 / 05期

关键词：

PLATELET-ACTIVATING-FACTOR; FREE FATTY-ACIDS; SPHINGOSINE; 1-PHOSPHATE; INJURY; APOPTOSIS; CELLS;

D O I：

10.1371/journal.pone.0303296

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Aim Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most prevalent liver diseases and is characterized by steatosis and the accumulation of bioactive lipids. This study aims to understand the specific lipid species responsible for the progression of liver fibrosis in MASH.Methods Changes in bioactive lipid levels were examined in the livers of MASH mice fed a choline-deficient diet (CDD). Additionally, sphingosine kinase (SphK)1 mRNA, which generates sphingosine 1 phosphate (S1P), was examined in the livers of patients with MASH.Results CDD induced MASH and liver fibrosis were accompanied by elevated levels of S1P and increased expression of SphK1 in capillarized liver sinusoidal endothelial cells (LSECs) in mice. SphK1 mRNA also increased in the livers of patients with MASH. Treatment of primary cultured mouse hepatic stellate cells (HSCs) with S1P stimulated their activation, which was mitigated by the S1P receptor (S1PR)2 inhibitor, JTE013. The inhibition of S1PR2 or its knockout in mice suppressed liver fibrosis without reducing steatosis or hepatocellular damage.Conclusion S1P level is increased in MASH livers and contributes to liver fibrosis via S1PR2.

引用

页数：14

共 37 条

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