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Smad AND Hepatitis

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https://www.readbyqxmd.com/read/28810242/mir-490-5p-suppresses-cell-proliferation-and-invasion-by-targeting-bub1-in-hepatocellular-carcinoma-cells
#1
Bin Xu, Tangpeng Xu, Huali Liu, Qian Min, Shidong Wang, Qibin Song
OBJECTIVE: To verify that miR-490-5p could influence hepatocellular carcinoma (HCC) cells' proliferation, invasion, cycle, and apoptosis by targeting BUB1. METHODS: Quantitative real time-PCR (QRT-PCR) was used to determine the miR-490-5p expression. Immunohistochemistry, qRT-PCR, and Western blot were employed to detect BUB1 and transforming growth factor-beta (TGFβ/Smad) signaling-related proteins expression in hepatic tissues and cells. The luciferase assay was used to confirm the targeting relationship between miR-490-5p and BUB1...
August 16, 2017: Pharmacology
https://www.readbyqxmd.com/read/28794616/schisandrin-b-attenuates-ccl4-induced-liver-fibrosis-in-rats-by-regulation-of-nrf2-are-and-tgf-%C3%AE-smad-signaling-pathways
#2
Qingshan Chen, Hai Zhang, Yan Cao, Ying Li, Sen Sun, Junping Zhang, Guoqing Zhang
Liver fibrosis is a major pathological feature of chronic liver diseases and there is no effective therapy program at present. Schisandrin B (Sch B) is the major bioactive ingredient of Schisandra chinensis, with antioxidative, anti-inflammatory, antitumor, and hepatoprotective properties. This study aimed to investigate the protective effect and related molecular mechanism of Sch B against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The in vivo therapeutic effect of Sch B on liver fibrosis induced by CCl4 was examined in rats...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28789951/hepatoprotective-activities-of-rosmarinic-acid-against-extrahepatic-cholestasis-in-rats
#3
Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Su-Lan Liao, Su-Tze Chou, Ching-Ping Yang, Chun-Jung Chen
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3...
August 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28761978/propolis-alleviates-concanavalin-a-induced-hepatitis-by-modulating-cytokine-secretion-and-inhibition-of-reactive-oxygen-species
#4
Fatma Mounieb, Laila Ramadan, El-Sayed Akool, Amany Balah
Viral hepatitis-induced oxidative stress accompanied by increased levels of transforming growth factor-β (TGF-β) and hepatic fibrosis are hallmarks of hepatitis C virus infection. The present study was designed to investigate the potential protective effect of propolis against liver injury induced by concanavalin A (Con A), a T-cell-dependent model that causes an immune-mediated hepatitis in a similar pattern to the one induced by viral infections. In the present study, rats were randomly divided into four groups...
July 31, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28739486/microrna-146a-5p-attenuates-liver-fibrosis-by-suppressing-profibrogenic-effects-of-tgf%C3%AE-1-and-lipopolysaccharide
#5
Yanting Zou, Yu Cai, Di Lu, Yi Zhou, Qunyan Yao, Shuncai Zhang
Liver fibrosis is characterized by proliferation and activation of hepatic stellate cells (HSCs). Transforming growth factor-β1 (TGFβ1) is crucial for liver fibrogenesis, and gut-derived endotoxin (LPS) also plays an important role in liver fibrogenesis. In the present study, we found that microRNA-146a-5p (miR-146a-5p) could regulate TGFβ1/Smad and LPS/NF-κB/Bambi pathways to attenuate liver fibrosis. Downregulated miR-146a-5p and upregulated level of LPS were found in liver of CCl4-treated rats. On cellular level, expression of miR-146a-5p is reduced during primary rat HSCs naturally activation and changed in response to TGFβ1 and/or LPS stimulation in primary rat HSCs and human HSC line LX-2...
July 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-beta-promotes-liver-tumorigenesis-in-mice-via-upregulation-of-snail
#6
Hyuk Moon, Hye-Lim Ju, Sook In Chung, Kyung Joo Cho, Jung Woo Eun, Suk Woo Nam, Kwang-Hyub Han, Diego F Calvisi, Simon Weonsang Ro
BACKGROUND & AIMS: Transforming growth factor beta (TGFB) suppresses early stages of tumorigenesis, but also contributes to migration and metastasis of cancer cells. A large number of human tumors contain mutations that inactivate its receptors, or downstream proteins such as Smad transcription factors, indicating that the TGFB signaling pathway prevents tumor growth. We investigated the effects of TGFB inhibition on liver tumorigenesis in mice. METHODS: C57BL/6 mice received hydrodynamic tail injections of transposons encoding HRAS(G12V) and a short hairpin RNA (shRNA) to downregulate p53, or those encoding HRAS(G12V) and MYC, or those encoding HRAS(G12V) and TAZ(S89), to induce liver tumor formation; mice were also given injections of transposons encoding SMAD7 or shRNA against SMAD2, SMAD3, SMAD4, or SNAI1 (Snail), with or without ectopic expression of Snail...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28713900/nlrc5-silencing-ameliorates-cardiac-fibrosis-by-inhibiting-the-tgf%C3%A2-%C3%AE-1-smad3-signaling-pathway
#7
Hongtao Zhou, Xuefang Yu, Guiming Zhou
The proliferation of cardiac fibroblasts (CFs) and excessive deposition of extracellular matrix are the predominant pathological characteristics of cardiac fibrosis. As the largest member of the nucleotide‑binding domain and leucine‑rich repeat (NLR) family, NLRC5 has been shown to be pivotal in the development of hepatic fibrosis. However, whether NLRC5 is involved in the pathogenesis of cardiac fibrosis remains to be elucidated. The present study aimed to investigate the role of NLRC5 and its mechanisms in regulating cardiac fibrosis...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710422/enmd-1068-inhibits-liver-fibrosis-through-attenuation-of-tgf-%C3%AE-1-smad2-3-signaling-in-mice
#8
Quan Sun, Yan Wang, Jie Zhang, Jing Lu
Protease-activated receptor 2 (PAR-2) plays an important role in the pathogenesis of liver fibrosis. We studied the effect of N1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine (ENMD-1068), a PAR-2 antagonist, on the development of CCl4-induced liver fibrosis in mice and activation of hepatic stellate cells (HSCs) isolated from the mice. Before CCl4 injection, the mice were injected intraperitoneally with either 25 mg/kg or 50 mg/kg ENMD-1068 or with 200 μL of the vehicle control twice per week for 4 weeks...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28702135/effect-of-tgf-%C3%AE-smad-signaling-pathway-blocking-on-expression-profiles-of-mir-335-mir-150-mir-194-mir-27a-and-mir-199a-of-hepatic-stellate-cells-hscs
#9
Parivash Davoodian, Mehrdad Ravanshad, Seyed Younes Hosseini, Sayyad Khanizadeh, Mohammad Almasian, Azim Nejati Zadeh, Hamed Esmaiili Lashgarian
AIM: The aim of this study was to determine the effect of inhibition of TGF-β/smad signaling on the expression profiles of miR-335, miR-150, miR-194, miR-27a, miR-199a of hepatic stellate cells (HSCs). BACKGROUND: Liver fibrosis is excessive deposition of extracellular matrix proteins due to ongoing inflammation and HSC activation that occurs in most types of chronic liver diseases. Recent studies have shown the importance of microRNAs in the pathogenesis of chronic liver diseases...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28689803/lipopolysaccharides-induce-smad2-phosphorylation-through-pi3k-akt-and-mapk-cascades-in-hsc-t6-hepatic-stellate-cells
#10
Ying-Hsien Kao, Po-Han Chen, Tin-Ya Wu, Yu-Chun Lin, Ming-Shian Tsai, Po-Huang Lee, Tzong-Shyuan Tai, Huoy-Rou Chang, Cheuk-Kwan Sun
AIMS: Endotoxemia and its pro-fibrogenic signaling play a significant role in the development of hepatic fibrosis. This study investigated whether lipopolysaccharide (LPS) directly activate cultured HSC-T6 hepatic stellate cells (HSCs) through triggering Smad-dependent pro-fibrogenic signaling pathway. MAIN METHODS: Direct cell counting and assays for cell proliferation and migration were used to measure the effects of LPS on HSC behaviors. Quantitative PCR, Western blot, and gelatin zymography were used to quantify the molecular effects of LPS on expression of HSC activation markers and signaling activity...
September 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28647476/substance-p-promotes-hepatic-stellate-cell-proliferation-and-activation-via-the-tgf-%C3%AE-1-smad-3-signaling-pathway
#11
Lei Peng, Xiaoqing Jia, Jianjian Zhao, Ruibing Cui, Ming Yan
Prolonged activation and proliferation of hepatic stellate cells (HSCs) usually results in the initiation and progression of liver fibrosis following injury. Recent studies have shown that Substance P (SP) participates in the development of fibrosis. However, whether SP is involved in liver fibrosis, especially in the activation and proliferation of HSCs, is largely unknown. In the present study, we measured the effects of a series of concentrations of SP on the cell viability and activation of HSC-T6 cells and LX2 cells...
August 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28623783/scoparone-attenuates-hepatic-stellate-cell-activation-through-inhibiting-tgf-%C3%AE-smad-signaling-pathway
#12
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...
September 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
#13
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...
August 15, 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
#14
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
#15
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...
August 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
#16
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
#17
NaveenKumar Perumal, MadanKumar Perumal, Devaraj Halagowder, NiranjaliDevaraj Sivasithamparam
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...
September 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
#18
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
#19
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
#20
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
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