An inducible sphingosine kinase 1 in hepatic stellate cells potentiates liver fibrosis

被引：2

作者：

Baek, Jin Sol ^{[1
]}

Lee, Ji Hyun ^{[1
]}

Kim, Ji Hye ^{[1
]}

Cho, Sam Seok ^{[1
,4
,7
,8
]}

Kim, Yun Seok ^{[2
,12
]}

Yang, Ji Hye ^{[3
]}

Shin, Eun Jin ^{[4
,5
,6
,7
,8
]}

Kang, Hyeon-Gu ^{[4
,5
,6
]}

Kim, Seok-Jun ^{[4
,5
,6
,7
,8
]}

Ahn, Sang-Gun ^{[9
]}

Park, Eun Young ^{[10
]}

Baek, Dong Jae ^{[10
]}

Yim, Sung-Kun ^{[11
]}

Kang, Keon Wook ^{[12
]}

Ki, Sung Hwan ^{[1
]}

Kim, Kyu Min ^{[4
,5
,6
,7
,8
]}

机构：

[1] Chosun Univ, Res Inst Pharmaceut Sci, Coll Pharm, MRC OSTRC, Gwangju 61452, South Korea

[2] Seoul Natl Univ, Coll Med, Dept Clin Pharmacol & Therapeut, Seoul 03080, South Korea

[3] Dongshin Univ, Coll Korean Med, Naju 58245, Jeollanam Do, South Korea

[4] Chosun Univ, Coll Nat Sci, Dept Biomed Sci, Gwangju 61452, South Korea

[5] Chosun Univ, Dept Integrat Biol Sci, Gwangju 61452, South Korea

[6] Chosun Univ, FOUR Educ Res Grp Age Associated Disorder Control, Gwangju 61452, South Korea

[7] Chosun Univ, Inst Well Aging Medicare, Gwangju 61452, South Korea

[8] Chosun Univ, G LAMP Project Grp, Gwangju 61452, South Korea

[9] Chosun Univ, Sch Dent, Dept Pathol, Gwangju 61452, South Korea

[10] Mokpo Natl Univ, Coll Pharm, Muan 58554, Jeonnam Do, South Korea

[11] Jeonnam Bioind Fdn, Marine Biotechnol Res Ctr, 21-7 Nonggongdanji 4Gil, Wandoeup 59108, South Korea

[12] Seoul Natl Univ, Inst Pharmaceut Sci, Coll Pharm & Res, Dept Pharm, Seoul, South Korea

来源：

BIOCHEMICAL PHARMACOLOGY | 2024年 / 229卷

基金：

新加坡国家研究基金会;

关键词：

Hepatic stellate cells; Sphingosine kinase; EGCG; GROWTH-FACTOR-BETA; TGF-BETA; GREEN TEA; COLLAGEN PRODUCTION; 1-PHOSPHATE; CANCER; EPIGALLOCATECHIN-3-GALLATE; SPHINGOSINE-1-PHOSPHATE; ACTIVATION; EXPRESSION;

D O I：

10.1016/j.bcp.2024.116520

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs. SphK1 was also increased in liver homogenates of carbon tetrachloride-treated or bile duct ligated mice and in transforming growth factor-beta (TGF-beta)-treated LX-2 cells. TGF-beta-mediated SphK1 induction was due to Smad3 signaling in LX-2 cells. SphK1 modulation altered the expression of liver fibrogenesis-related genes. This SphK1-mediated profibrogenic effect was dependent on SphK1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor signaling through ERK. Epigallocatechin gallate blocked TGF-beta-induced SphK1 expression and hepatic fibrogenesis by attenuating Smad and MAPK activation. SphK1 induced by TGF-beta facilitates HSC activation and liver fibrogenesis, which is reversed by epigallocatechin gallate. Accordingly, SphK1 and related signal transduction may be utilized to treat liver fibrosis.

引用

页数：13

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