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Smad AND Hepatitis

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https://www.readbyqxmd.com/read/28623783/scoparone-attenuates-hepatic-stellate-cell-activation-through-inhibiting-tgf-%C3%AE-smad-signaling-pathway
#1
Xing Liu, Xiuxia Zhao
Activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. Scoparone, a major constituent isolated from Artemisia capillaris, was reported to possess hepatoprotective effect. However, the role of scoparone in liver fibrosis remains unknown. In the present study, we investigated the effects of scoparone on liver fibrosis in HSCs. Our results demonstrated that scoparoene inhibited the proliferation of HSCs exposed to transforming growth factor (TGF)-β1. In addition, scoparoene significantly suppressed TGF-β1-induced the expression of α-smooth muscle actin (α-SMA) and collagen I in HSC-T6 cells, as well as attenuated the expression of NADPH oxidase (NOX) isoforms expression and ROS production in TGF-β1-stimialted HSC-T6 cells...
June 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28623179/modulation-of-tgf-%C3%AE-smad-and-erk-signaling-pathways-mediates-the-anti-fibrotic-effect-of-mirtazapine-in-mice
#2
Dalia M El-Tanbouly, Walaa Wadie, Rabab H Sayed
Serotonin (5-HT) has been implicated as a key driver of liver fibrosis, acting via 5-HT2 receptor activation in the hepatic stellate cells. The current study was conducted to investigate the effects of mirtazapine, a 5-HT2A antagonist, in a mouse model of liver fibrosis. Mice received thioacetamide (TAA, 150mg/kg/biweekly, ip) for nine successive weeks for induction of liver fibrosis. Administration of mirtazapine significantly improved the plasma aminotransferases, reduced hepatic 5-HT concentration and ameliorated TAA-induced liver fibrosis, as demonstrated by reduced portal blood pressure, liver procollagen I content and α alpha smooth muscle actin expression...
June 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28599486/knockout-of-kr%C3%A3-ppel-like-factor-10-suppresses-hepatic-cell-proliferation-in-a-partially-hepatectomized-mouse-model
#3
Seung-Ho Heo, Eui-Suk Jeong, Kyoung-Sun Lee, Jin-Hee Seo, Woon-Kyu Lee, Yang-Kyu Choi
The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-β (TGF-β)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Krüppel-like factor 10 (KLF10) has been reported to activate the TGF-β/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28585096/cellular-citrate-levels-establish-a-regulatory-link-between-energy-metabolism-and-the-hepatic-iron-hormone-hepcidin
#4
Ana Rita da Silva, Joana Neves, Katarzyna Mleczko-Sanecka, Amol Tandon, Sven W Sauer, Matthias W Hentze, Martina U Muckenthaler
Expression of the hepatic peptide hormone hepcidin responds to iron levels via BMP/SMAD signaling, to inflammatory cues via JAK/STAT signaling, to the nutrient-sensing mTOR pathway, as well as to proliferative signals and gluconeogenesis. Here, we asked the question whether hepcidin expression is altered by metabolites generated by intermediary metabolism. To identify such metabolites, we took advantage of a comprehensive RNAi screen, which revealed effectors involved in citrate metabolism. We show that the inhibition of citrate-consuming enzymes increases hepcidin mRNA expression in primary murine hepatocytes...
June 5, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28561587/protective-effects-of-functional-chicken-liver-hydrolysates-against-liver-fibrogenesis-antioxidation-anti-inflammation-and-antifibrosis
#5
Po-Ju Chen, Jung-Kai Tseng, Yi-Ling Lin, Yi-Hsieng Samuel Wu, Yi-Tse Hsiao, Jr-Wei Chen, Yi-Chen Chen
Via an assay using an Amino Acid Analyzer, pepsin-digested chicken liver hydrolysates (CLHs) contain taurine (365.57 ± 39.04 mg/100 g), carnosine (14.03 ± 1.98 mg/100 g), and anserine (151.58 ± 27.82 mg/100 g). This study aimed to evaluate whether CLHs could alleviate thioacetamide (TAA)-induced fibrosis. A dose of 100 mg TAA/kg BW significantly increased serum liver damage indices and liver cytokine contents. Cell infiltration and monocytes/macrophages in livers of TAA-treated rats were illustrated by the H&E staining and immunohistochemical analysis of cluster of differentiation 68 (CD68, ED1), respectively...
June 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28552397/morin-attenuates-diethylnitrosamine-induced-rat-liver-fibrosis-and-hepatic-stellate-cell-activation-by-co-ordinated-regulation-of-hippo-yap-and-tgf-%C3%AE-1-smad-signaling
#6
Perumal NaveenKumar, Perumal MadanKumar, Halagowder Devaraj, Sivasithamparam NiranjaliDevaraj
Despite great progress in understanding the activation of hepatic stellate cells (HSCs) during liver fibrosis, therapeutic approaches to inhibit HSC activation remain very limited. Recent reports highlight Yes-associated protein (Yap) and transforming growth factor-β1 (TGF-β1) as critical regulators of HSC activation and henceforth a compound targeting Hippo/Yap and TGF-β1/Smad pathways would be a potential anti-fibrotic candidate. Morin, a dietary flavonoid, was earlier reported to inhibit HSC proliferation and induction of apoptosis of cultured HSCs, mainly by suppressing Wnt/β-catenin and NF-κB signaling, but its effect on Hippo/Yap and TGF-β1/Smad pathways was not determined...
May 25, 2017: Biochimie
https://www.readbyqxmd.com/read/28518142/mir-130a-3p-attenuates-activation-and-induces-apoptosis-of-hepatic-stellate-cells-in-nonalcoholic-fibrosing-steatohepatitis-by-directly-targeting-tgfbr1-and-tgfbr2
#7
Yang Wang, Jinghua Du, Xuemin Niu, Na Fu, Rongqi Wang, Yuguo Zhang, Suxian Zhao, Dianxing Sun, Yuemin Nan
Nonalcoholic fibrosing steatohepatitis is a uniform process that occurs throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been shown to be involved in the biological processes, but the role and molecular mechanism of miRNAs in NAFLD are not entirely clear. In this study, we observed a significant reduction in the expression of miR-130a-3p in livers of a mouse model with fibrosis induced by a methionine-choline-deficient diet, of NAFLD patients, and in activated hepatic stellate cells (HSCs)...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28504959/casticin-attenuates-liver-fibrosis-and-hepatic-stellate-cell-activation-by-blocking-tgf-%C3%AE-smad-signaling-pathway
#8
Ling Zhou, Xiaoying Dong, Linlin Wang, Lanlan Shan, Ting Li, Wanfu Xu, Yan Ding, Mingqiang Lai, Xiaojun Lin, Meng Dai, Xiaochun Bai, Chunhong Jia, Hang Zheng
Although many advances have been made in understanding the pathogenesis of liver fibrosis, few options are available for treatment. Casticin, one of the major flavonoids in Fructus Viticis extracts, has shown hepatoprotective potential, but its effects on liver fibrosis are not clear. In this study, we investigated the antifibrotic activity of casticin and its underlying mechanism in vivo and in vitro. Male mice were injected intraperitoneally with carbon tetrachloride (CCl4) or underwent bile duct ligation (BDL) to induce liver fibrosis, followed by treatment with casticin or vehicle...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498453/the-inhibition-of-microrna-15a-suppresses-hepatitis%C3%A2-b-virus-associated-liver-cancer-cell-growth-through-the-smad-tgf-%C3%AE-pathway
#9
Yan Wang
In the present study, the role of microRNA‑15a (miR‑15a) was investigated in hepatitis B virus (HBV)‑associated liver cancer. The results revealed that the expression levels of miR-15a were increased in HBV-associated liver cancer tissues compared with the levels in normal tumor‑adjacent tissues. Moreover, Smad-7 protein expression in patients with HBV-associated liver cancer was higher than that in normal tumor-adjacent tissues. In addition, miR-15a expression and Smad-7 protein expression were increased in HepG2 hepatocellular carcinoma cells compared with that noted in L-02 normal hepatocytes...
May 2, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28494543/-effects-of-anluohuaxianwan-on-transforming-growth-factor-%C3%AE-1-and-related-signaling-pathways-in-rats-with-carbon-tetrachloride-induced-liver-fibrosis
#10
W Lu, Y H Gao, Z Z Wang, Y S Cai, Y Q Yang, Y Q Miao, F Pei, X E Liu, H Zhuang
Objective: The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection. However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This study used a rat model of carbon tetrachloride (CCl(4))-induced liver fibrosis to explore the potential antifibrogenic mechanisms of ALHXW. Methods: Twenty-seven male Wistar rats were randomly assigned to control group, model group, and treatment group (n = 9 per group). Rats in the model and treatment group were injected intraperitoneally with 40% CCl(4)(2 ml/kg), and rats in the control group were administered saline twice a week for 6 weeks...
April 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28437886/activation-of-imidazoline-i1-receptor-by-moxonidine-regulates-the-progression-of-liver-fibrosis-in-the-nrf2-dependent-pathway
#11
Wenfeng Zhang, Xuanfei Li, Yanmin Liu, Hao Chen, Jianping Gong
Imidazoline I1 receptor (I1R) has been recognized as a promising target in the treatment of many diseases, but little is known about its function in liver fibrogenesis. This study aimed to investigate the effect of I1R activation on the development and progression of liver fibrosis. The results showed that I1R expression was decreased in the livers of both patients and mice with liver fibrosis, and in TGF-β-treated hepatic stellate cells (HSCs). Activation of I1R by moxonidine (MOX) significantly inhibited the progression of liver fibrosis in carbon tetrachloride-induced mice and attenuated the activation of HSCs and kupffer cells...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28423499/imidazoline-i2-receptor-inhibitor-idazoxan-regulates-the-progression-of-hepatic-fibrosis-via-akt-nrf2-smad2-3-signaling-pathway
#12
Li Xuanfei, Chen Hao, Yi Zhujun, Liu Yanming, Gong Jianping
Liver fibrosis is a global health problem and its relationship with imidazoline I2 receptor has not been reported. This study aimed to investigate the effects and underlying mechanisms of imidazoline I2 receptor (I2R) inhibitor idazoxan (IDA) on carbon tetrachloride (CCl4)-induced liver fibrosis. In vivo liver fibrosis in mice was induced by intraperitoneally injections of CCl4 for eight weeks, and in vitro studies were performed on activated LX2 cells treated with transforming growth factor-β (TGF-β). Our results showed that IDA significantly improved liver inflammation, ameliorated hepatic stellate cells activation and reduced collagen accumulation by suppressing the pro-fibrogenic signaling of TGF-β/Smad...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406452/suppression-of-hepatic-epithelial-to-mesenchymal-transition-by-melittin-via-blocking-of-tgf%C3%AE-smad-and-mapk-jnk-signaling-pathways
#13
Ji-Hyun Park, Byoungduck Park, Kwan-Kyu Park
Transforming growth factor (TGF)-β1 plays a crucial role in the epithelial-to-mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC), which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a major component of bee venom and is effective in rheumatoid arthritis, pain relief, cancer cell proliferation, fibrosis and immune modulating activity. In this study, we found that MEL inhibits hepatic EMT in vitro and in vivo, regulating the TGFβ/Smad and TGFβ/nonSmad signaling pathways...
April 13, 2017: Toxins
https://www.readbyqxmd.com/read/28405682/apamin-suppresses-biliary-fibrosis-and-activation-of-hepatic-stellate-cells
#14
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Yoon-Yub Park, Kyung Duck Park, Kwan-Kyu Park
Cholestatic liver disease is characterized by the progressive destruction of biliary epithelial cells (BECs) followed by fibrosis, cirrhosis and liver failure. Activated hepatic stellate cells (HSCs) and portal fibroblasts are the major cellular effectors of enhanced collagen deposition in biliary fibrosis. Apamin, an 18 amino acid peptide neurotoxin found in apitoxin (bee venom), is known to block Ca2+-activated K+ channels and prevent carbon tetrachloride-induced liver fibrosis. In the present study, we aimed to ascertain whether apamin inhibits biliary fibrosis and the proliferation of HSCs...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28364097/-effect-of-lamivudine-and-silymarin-on-liver-fibrosis-relevant-factors-in-hbv-transgenic-mice-with-alcohol-drinking
#15
Juanjuan Huang, Shikun Liu, Zuojun Li, Libo Cao, Linqi Ouyang
To observe the role of lamividine and silymarin preventing and curing liver fibrosis-relevant factors induced by alcohol drinking in hepatitis B virus (HBV) transgenic mice (Tg mice).
 Methods: Forty HBV-Tg BALB/C mice with 1.3 copy were randomly divided into 4 groups: a control group, a model group, a lamivudine group and a silymarin group. Tg mice in control group were treated with normal saline via intragastric administration; Tg-mice in the model group were treated with 50% alcohol (5 mL/kg) once a day via intragastric administration; while Tg-mice in lamivudine group and silymarin group were treated with alcohol (5 mL/kg) plus laminvudine (100 mg/kg) and silymarin (200 mg/kg) once a day via intragastric administration respectively...
March 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28352366/prolyl-oligopeptidase-attenuates-hepatic-stellate-cell-activation-through-induction-of-smad7-and-ppar-%C3%AE
#16
Da Zhou, Jing Wang, Ling-Nan He, Bing-Hang Li, Yong-Nian Ding, Yuan-Wen Chen, Jian-Gao Fan
Prolyl oligopeptidase (POP) is a serine endopeptidase widely distributed in vivo with high activity in the liver. However, its biological functions in the liver have remained largely elusive. A previous study by our group has shown that POP produced N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) and thereby exerted an anti-fibrogenic effect on hepatic stellate cells (HSCs) in vitro. It was therefore hypothesized that POP may affect the activation state of HSCs and has an important role in liver fibrosis. The HSC-T6 immortalized rat liver stellate cell line was treated with the POP inhibitor S17092 or transfected with recombinant lentivirus to overexpress POP...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28345552/relationship-between-hepatitis-c-virus-infection-and-iron-overload
#17
REVIEW
Dong-Mei Zou, Wan-Ling Sun
OBJECTIVE: The aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle. DATA SOURCES: This review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication"...
April 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28320106/ctrp3-attenuates-hepatic-stellate-cell-activation-through-transforming-growth-factor-%C3%AE-smad-signaling-pathway
#18
Chuantao Cheng, Shuo Yu, Ran Kong, Qinggong Yuan, Yuefeng Ma, Wenbin Yang, Gang Cao, Liyi Xie
Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of liver fibrosis. C1q/tumor necrosis factor-related protein 3 (CTRP3), a member of CTRPs, was involved in fibrosis. However, little is known about the role of CTRP3 in liver fibrosis. This study aimed to determine its role in liver fibrosis and explore the possible mechanism. Our results demonstrated that CTRP3 was lowly expressed in liver fibrosis tissues and activated HSCs. Overexpression of CTRP3 inhibited the proliferation and migration of HSCs, as well as suppressed the expression of extracellular matrix (ECM) in transforming growth factor-β1 (TGF-β1)-stimulated HSC-T6 cells...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28181132/anti-tgf%C3%AE-1-receptor-inhibitor-mediates-the-efficacy-of-the-human-umbilical-cord-mesenchymal-stem-cells-against-liver-fibrosis-through-tgf%C3%AE-1-smad-pathway
#19
Ji Xuan, Wang Feng, Zheng-Tao An, Jian Yang, Hua-Bing Xu, Jing Li, Zhi-Fei Zhao, Wei Wen
The aim of the current investigation was to evaluate the anti-fibrosis potential of human umbilical cord mesenchymal stem cells (hUC-MSCs) and further to explore some of its underlying mechanisms. Hepatic fibrosis mice model was induced by CCl4. Liver function parameters in serum and fibrosis-associated markers in tissues were detected. Moreover, SB-431542, an anti-TGFβ-1 receptor inhibitor, was employed in vitro to reveal the underlying mechanism of TGFβ-1/Smad pathway on hUC-MSCs against liver fibrosis...
May 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28154170/transforming-growth-factor-%C3%AE-tgf-%C3%AE-directly-activates-the-jak1-stat3-axis-to-induce-hepatic-fibrosis-in-coordination-with-the-smad-pathway
#20
Liu-Ya Tang, Mary Heller, Zhaojing Meng, Li-Rong Yu, Yi Tang, Ming Zhou, Ying E Zhang
Transforming growth factor-β (TGF-β) signals through both SMAD and non-SMAD pathways to elicit a wide array of biological effects. Existing data have shown the association and coordination between STATs and SMADs in mediating TGF-β functions in hepatic cells, but it is not clear how STATs are activated under these circumstances. Here, we report that JAK1 is a constitutive TGFβRI binding protein and is absolutely required for phosphorylation of STATs in a SMAD-independent manner within minutes of TGF-β stimulation...
March 10, 2017: Journal of Biological Chemistry
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