Novel cytisine derivatives exert anti-liver fibrosis effect via PI3K/Akt/Smad pathway

2019 ◽  
Vol 90 ◽  
pp. 103032 ◽  
Author(s):  
Sheng Tang ◽  
Yinghong Li ◽  
Yunyang Bao ◽  
Zhiting Dai ◽  
Tianyu Niu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Smad Pathway ◽  
Cytisine Derivatives

scholarly journals Notch signaling mediated by TGF-β/Smad pathway in concanavalin A-induced liver fibrosis in rats

2017 ◽  
Vol 23 (13) ◽  
pp. 2330 ◽  
Author(s):  
Yi Wang ◽  
Ruo-Wu Shen ◽  
Bing Han ◽  
Zhen Li ◽  
Le Xiong ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Notch Signaling ◽  
Concanavalin A ◽  
Smad Pathway

MCP-1-Induced Protein 1 Relieved Liver Fibrosis by Suppressing the TGF-β/Smad Pathway and Epithelial and Mesenchymal Transition

2019 ◽  
Vol 9 (10) ◽  
pp. 1355-1361
Author(s):  
Hongjia Sun ◽  
Chen Zhang ◽  
Yumei Huang ◽  
Ting Wang ◽  
Liqiong Yao
Keyword(s):  
Animal Model ◽  
Liver Fibrosis ◽  
Western Blotting ◽  
Liver Diseases ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Collagen I ◽  
Severe Liver ◽  
Smad Pathway ◽  
Mesenchymal Transition

Liver fibrosis is a kind of lesion caused by damaged hepatocytes that may contribute to diverse severe liver diseases if not treated promptly. MCPIP1 was a protein which could protect the liver from ischemia reperfusion and LPS induced inflammation response. But whether MCPIP1 could alleviate liver fibrosis was not revealed. In our research, we used CCl4 on rats to construct the liver fibrosis animal model. Moreover, TGF-β1 was used to induce LX2 cells so as to establish the fibrotic cell model. Then we detected the expression of MCPIP1 in these tissues and cells. After that, the cellular morphology of LX2 cells was observed and the levels of α-SMA, collagen I, desmin, E-cadherin, Slug, N-cadherin, p-Smad3, Smad3 and Smad4 in LX2 cells were detected with western-blotting. The results showed that the expression of MCPIP1 was decreased in the liver fibrosis tissues and that TGF-β1 induced LX2 cells. In addition, the shape of TGF-β1 induced LX2 cells to gradually become spindle shaped. Furthermore, the expression of α-SMA, collagen I, desmin, Slug, N-cadherin, p-Smad3 and Smad4 was enhanced in TGF-β1-induced LX2 cells. However, the levels of these proteins were further suppressed after the overexpression of MCPIP1. MCPIP1 alleviated liver fibrosis by inhibiting the TGF-β/Smad pathway and EMT which was induced by the TGF-β/Smad pathway.

Imidacloprid-induced liver fibrosis in quails via activation of the TGF-β1/Smad pathway

2020 ◽  
Vol 705 ◽  
pp. 135915 ◽  
Author(s):  
Yueying Lv ◽  
Qizheng Bing ◽  
Zhanjun Lv ◽  
Jiangdong Xue ◽  
Siyu Li ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Smad Pathway ◽  
Tgf Β1

scholarly journals Obacunone Attenuates Liver Fibrosis with Enhancing Anti-Oxidant Effects of GPx-4 and Inhibition of EMT

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 318
Author(s):  
Yongquan Bai ◽  
Wenwen Wang ◽  
Li Wang ◽  
Lirong Ma ◽  
Dongsheng Zhai ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Underlying Mechanism ◽  
Major Pathway ◽  
Smad Pathway ◽  
Anti Oxidant ◽  
Mice Liver ◽  
Excessive Oxygen

Obacunone, a limonin triterpenoid extracted from Phellodendronchinense Schneid or Dictamnus dasycarpusb Turcz plant, elicits a variety of pharmacological effects such as anti-inflammatory, anti-neoplastic, anti-oxidation, and anti-lung-fibrosis ones. However, the anti-fibrotic effect of obacunone and the detailed underlying mechanism in liver fibrosis remain unclear. Liver fibrosis is a debilitating disease threatening human health. Transforming growth factor (TGF)-β/P-Smad is a major pathway of fibrosis featured with epithelia mesenchymal transformations (EMT) and collagen depositions, accompanying with excessive oxygen-free radicals. Nrf-2 acts as a key anti-oxidative regulator driving the expressions of various antioxidant-related genes. Glutathionperoxidase-4 (GPx-4) is a member of the glutathione peroxidase family that directly inhibits phospholipid oxidation to alleviate oxidative stress. In the present study, we aimed to explore the role of obacunone in mouse liver fibrosis model induced by carbon tetrachloride (CCl4) and in hepatic stellate cells (LX2 cell line) challenging with TGF-β. Obacunone demonstrated potent ameliorative effects on liver fibrosis both in activated LX2 and in mice liver tissues with reduced levels of α-SMA, collagen1, and vimentin. Obacunone also remarkably suppressed the TGF-β/P-Smad signals and EMT process. Meanwhile, obacunone exerted a potent anti-oxidation effect by reducing the levels of reactive oxygen species (ROS) in both models. The antioxidant effect of obacunone was attributed to the activation of GPx-4 and Nrf-2. In addition, the therapeutic effect of obacunone on LX2 cells was significantly removed in vitro plus with GPx-4 antagonist RSL3, in parallel with the re-elevated levels of ROS. Thus, we demonstrate that obacunone is able to attenuate liver fibrosis via enhancing GPx-4 signal and inhibition of the TGF-β/P-Smad pathway and EMT process.

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