相关实验视频

Updated: Aug 11, 2026

Seven Steps to Stellate Cells

Seven Steps to Stellate Cells

Published on: May 10, 2011

抑制MASH纤维化进展,通过阻断肝星细胞中糖酸-GPR91信号传递

Li Xie¹, Hui Chen¹, Li Zhang¹

¹Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

Hepatology (Baltimore, Md.)

|May 20, 2025

概括

阻断肝星细胞中的酸盐受体GPR91可以阻止在代谢功能障碍相关的脂肪肝炎 (MASH) 中肝纤维化进展. 这种有针对性的方法抑制了HSC激活,并防止了细胞亡,为MASH提供了一个有前途的治疗策略.

科学领域:

肝病学肝病学是一种肝病学.
分子生物学分子生物学
纤维化研究纤维化研究

背景情况:

酸盐受体GPR91在代谢功能障碍相关的脂肪肝炎 (MASH) 诱导的纤维化期间,在肝星细胞 (HSC) 中被上调.
在MASH纤维回归中GPR91阻断的体内证据有限.

研究的目的:

研究HSC特定的GPR91在MASH相关的肝纤维化中的作用.
确定阻断GPR91信号是否会导致MASH模型中的纤维回归.

主要方法:

使用胆缺乏氨基酸定义饮食与脂多糖 (CDAA-LPS) 或高脂肪/高卡路里饮食与高果糖/高葡萄糖 (HFCD-HF/G) 诱导MASH模型.
实验涉及野生型 (WT) 鼠和HSC特有的GPR91淘汰赛 (HSC-GPR91-KO) 鼠.
使用了酸盐和体外人类HSC刺激.

主要成果:

在WT小鼠中结加重的纤维化,增加原蛋白和氧.
与在HFCD-HF/G条件下的WT小鼠相比,HSC-GPR91-KO小鼠显示肝纤维化改善.
酸盐刺激通过ERK/c-jun/Smad3激活了HSC,并通过NF-κB信号传递抑制了亡.

结论:

在MASH模型中,HSC特有的GPR91缺乏有效地阻止了肝纤维化.
GPR91阻断通过不同的途径起作用:抑制HSC激活和防止细胞亡.
对于MASH-纤维化进展,GPR91是一个有前途的治疗标.

关键词:

细胞灭亡 (apoptosis) 是一种死亡的过程.在ERK/c-jun-smad3轴上纤维化纤维化纤维化在 GPR91 中使用.肝脏的星状细胞是什么与代谢功能障碍相关的脂肪肝肝炎.在cAMP-CREB-NF-κB信号通路中.

更多相关视频

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

Published on: February 10, 2015

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis

Published on: March 11, 2017

相关概念视频

GPCR Desensitization

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are typically...

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...