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Smad AND Hepatitis

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28153731/positive-feedback-loop-of-yb-1-interacting-with-smad2-promotes-liver-fibrosis
#15
Panpan Xiong, Jun Zhang, Diannan Xu, Jie Zhu, Wenshuai Li, Jie Liu, Fei Liu
Y-box binding protein (YB-1), known as a multifunctional cellular protein in various biological processes, was recently reported to be associated with liver fibrosis. The critical role of TGF-β/Smad signaling pathway in stimulating the transcription of fibrotic genes in fibroblasts have already been identified, however, whether and how YB-1 modulated liver fibrosis via TGF-β/Smad signaling pathway remains largely unknown. In our previous study, we proved that ectopic TGF-β was associated with YB-1 expression...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28147890/astragaloside-iv-synergizes-with-ferulic-acid-to-suppress-hepatic-stellate-cells-activation-in-vitro
#16
Haiying Dong, Hongyan Guo, Yini Liang, Xing Wang, Yingcai Niu
Because hepatic fibrosis usually involves more than one pathological process, combination therapy with modalities that target aberrant signaling cascade in activated hepatic stellate cells (HSCs) represents an alternative strategy. This study evaluates the hypothesis that astragaloside IV (AS-IV) and ferulic acid (FA) synergize to inhibit HSCs activation via simultaneous activating nuclear factor erythroid-2-related factor-2 (Nrf2) and blocking transforming growth factor-β (TGF-β) pathways. The combination of FA and AS-IV, hereafter referred to as the AS-IV/FA, at suboptimal concentrations synergistically inhibited HSCs activation, as measured by expressions of α-smooth muscle actin (α-SMA), collagen α type I (Col I) and fibronectin...
February 2017: Free Radical Research
https://www.readbyqxmd.com/read/28115038/identification-of-mfge8-in-mesenchymal-stem-cell-secretome-as-an-anti-fibrotic-factor-in-liver-fibrosis
#17
Yu Jin Jang, Su Yeon An, Jong-Hoon Kim
The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the TGFβ/Smad-signaling...
February 2017: BMB Reports
https://www.readbyqxmd.com/read/28086769/effect-of-ginseng-extract-on-the-tgf-%C3%AE-1-signaling-pathway-in-ccl4-induced-liver-fibrosis-in-rats
#18
Mohamed M Hafez, Sherifa S Hamed, Manal F El-Khadragy, Zeinab K Hassan, Salim S Al Rejaie, Mohamed M Sayed-Ahmed, Naif O Al-Harbi, Khalid A Al-Hosaini, Mohamed M Al-Harbi, Ali R Alhoshani, Othman A Al-Shabanah, Shakir Dekhal Alsharari
BACKGROUND: Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks...
January 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27991776/capsaicin-inhibits-dimethylnitrosamine-induced-hepatic-fibrosis-by-inhibiting-the-tgf-%C3%AE-1-smad-pathway-via-peroxisome-proliferator-activated-receptor-gamma-activation
#19
Jae Ho Choi, Sun Woo Jin, Chul Yung Choi, Hyung Gyun Kim, Gi Ho Lee, Yong An Kim, Young Chul Chung, Hye Gwang Jeong
Capsaicin (CPS) exerts many pharmacological effects, but any possible influence on liver fibrosis remains unclear. Therefore, we evaluated the inhibitory effects of CPS on dimethylnitrosamine (DMN) and TGF-β1-induced liver fibrosis in rats and hepatic stellate cells (HSCs). CPS inhibited DMN-induced hepatotoxicity, NF-κB activation, and collagen accumulation. CPS also suppressed the DMN-induced increases in α-SMA, collagen type I, MMP-2, and TNF-α. In addition, CPS inhibited DMN-induced TGF-β1 expression (from 2...
January 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27990439/effect-of-exogenous-fetuin-a-on-tgf-%C3%AE-smad-signaling-in-hepatic-stellate-cells
#20
Yulai Zhou, Shuang Yang, Pan Zhang
Objective. To explore the effects of low concentration of exogenous fetuin-A intervention on TGF-β1 induced LX2 cells through detection of the expression of mRNA and protein of Smad2, Smad3, and Smad7. Methods. MTT assay was used to detect the LX2 cells proliferation and the regression equation calculating software was applied to determine IC50 of fetuin-A. RT-PCR was used to determine the relative content of Smad2, Smad3, and Smad7 mRNA in LX2 cells. Western blot was used to detect the LX2 cells relative content of Smad2, Smad3, Smad7 protein expression, respectively...
2016: BioMed Research International
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