安洛丁尼布通过调节转化生长因子β1/Smad3信号通路来减轻肝纤维化
Ye-Ting Wu1,2, Qi-Zhe Li3, Xue-Ke Zhao2
1Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, No 188, Shizi Street, Suzhou, 215000, Jiangsu, China.
Digestive diseases and sciences
|September 7, 2023
概括
安洛丁尼布通过TGF-β1/Smad3通路抑制肝星细胞激活,有效地逆转肝纤维化. 这种FDA批准的药物在治疗肝损伤和炎症方面表现有前途.
科学领域:
- 肝病学和纤维化研究研究.
- 药理学和药物发现
- 细胞生物学和信号传递
背景情况:
- 肝星细胞 (HSC) 的过度活化对肝纤维化进展至关重要.
- 转化生长因子-β1 (TGF-β1) 是HSCs的主要激活剂.
- 了解HSC激活机制是开发抗纤维菌疗法的关键.
研究的目的:
- 为了研究anlotinib在减轻碳四化物 (CCl4) 诱导的小鼠肝纤维化的疗效.
- 阐明anlotinib的抗纤维化机制,重点关注TGF-β1信号传递.
主要方法:
- 在体外研究中使用了用TGF-β1.1治疗的LX-2人类肝细胞形细胞.
- 试验包括细胞毒性,细胞迁移 (Transwell),以及对I型原蛋白,α-SMA和p-Smad3.3的西部斑点.
- 在体内研究中使用了CCl4诱导的肝纤维化小鼠模型,并进行了他的病理学分析 (H&E,马森三色素,IHC).
主要成果:
- 安洛丁尼布抑制了LX-2细胞中TGF-β1诱导的 I型原蛋白,α-SMA和p-Smad3的增加.
- 安洛丁尼布在体外抑制了LX-2细胞的迁移和繁殖能力.
- 在体内,安洛替尼治疗显著降低了CCl4治疗小鼠的纤维化 (F4至F2),炎症评分,ALT和AST水平.
结论:
- 安洛丁尼布通过抑制TGF-β1 / Smad3信号通路来抑制肝纤维化,从而减少HSC激活.
- 安洛丁尼布显示出对CCl4诱导的肝损伤的保护作用,包括炎症和纤维化逆转.
- 安洛丁尼布是一种FDA批准的多向氨酸激酶抑制剂,具有作为慢性肝病治疗剂的潜力.
更多相关视频
08:56Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
52.4K
10:21Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
7.2K
相关概念视频
01:16TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
01:22PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
01:24Liver Regeneration
3.3K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.3K