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https://www.readbyqxmd.com/read/28936800/evodiamine-ameliorates-liver-fibrosis-in-rats-via-tgf-%C3%AE-1-smad-signaling-pathway
#1
Dongmei Yang, Li Li, Shanjun Qian, Lixin Liu
Liver fibrosis is considered to be a result of chronic liver pathological changes, and hepatic stellate cells (HSCs) play an important role during this process. Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities. This study focused on the effects of evodiamine on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and HSCs in vitro via the TGF-β1/Smad signaling pathway. A liver fibrosis rat model was established by the intraperitoneal injection of CCl4 (3 ml/kg, 30% in olive oil)...
September 21, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28929107/microrna-195-activates-hepatic-stellate-cells-in-vitro-by-targeting-smad7
#2
Li-Ying Song, Yu-Tao Ma, Cui-Fang Wu, Chun-Jiang Wang, Wei-Jin Fang, Shi-Kun Liu
BACKGROUND AND AIM: Aberrant activation of the TGF-β1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs. The aim of this study was to investigate the role of miRNA-195 in HSCs activation. METHODS: A liver fibrotic rat model induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195. The expression levels of miR-195, Smad7, and α-SMA in HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28918026/anti-fibrotic-effects-of-synthetic-oligodeoxynucleotide-for-tgf-%C3%AE-1-and-smad-in-an-animal-model-of-liver-cirrhosis
#3
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Mi-Gyeong Gwon, Hyemin Gu, Yoon-Yub Park, Kwan-Kyu Park
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28915589/casticin-attenuates-liver-fibrosis-and-hepatic-stellate-cell-activation-by-blocking-tgf-%C3%AE-smad-signaling-pathway
#4
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893916/the-role-of-activins-in-hepcidin-regulation-during-malaria
#5
Natasha Spottiswoode, Andrew E Armitage, Andrew R Williams, Alex J Fyfe, Sumi Biswas, Susanne H Hodgson, David Llewellyn, Prateek Choudhary, Simon J Draper, Patrick Duffy, Hal Drakesmith
Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in Plasmodium berghei murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation...
September 11, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28864168/liuweiwuling-tablets-attenuate-bdl-induced-hepatic-fibrosis-via-modulation-of-tgf-%C3%AE-smad-and-nf-%C3%AE%C2%BAb-signaling-pathways
#6
Huimin Liu, Fang Dong, Guangquan Li, Ming Niu, Congen Zhang, Yanzhong Han, Lanzhi He, Ping Yin, Bin Wang, Xiuxiu Sang, Ruishen Li, Jiabo Wang, Zhaofang Bai, Xiaohe Xiao
ETHNOPHARMACOLOGICAL RELEVANCE: Liuweiwuling (LWWL) tablets contain a six-herb Chinese formula and are commonly prescribed to facilitate nourishment of the liver and kidneys, clear away toxic materials and activate blood circulation. Administration of LWWL is well known for its protective effects on the liver and its capacity to confer long-term stability in patients exhibiting reduced transaminase levels. Clinical studies have reported that LWWL can also be used for the treatment of liver fibrosis with associated treatment regimens resulting in a concomitant reduction in transforming growth factor β1 (TGF-β1) levels in the serum of patients with hepatic fibrosis...
August 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28857040/hepatitis-c-virus-down-regulates-serpine1-pai-1-expression-to-facilitate-its-replication
#7
Chee-Hing Yang, Hui-Chun Li, Tzu-Shan Ku, Pi-Ching Wu, Yung-Ju Yeh, Ju-Chien Cheng, Teng-Yi Lin, Shih-Yen Lo
Identification of host factors involved in viral replication is critical for understanding the molecular mechanism of viral replication and pathogenesis. Genes differentially expressed in HuH-7 cells with or without a hepatitis C virus (HCV) sub-genomic replicon were screened by microarray analysis. SERPINE1/PAI-1 was found to be down-regulated after HCV infection in this analysis. Down-regulation of SERPINE1/PAI-1 expression at the transcriptional level was verified by the real-time reverse transcriptase (RT)-PCR assay...
September 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28839277/quercetin-prevents-hepatic-fibrosis-by-inhibiting-hepatic-stellate-cell-activation-and-reducing-autophagy-via-the-tgf-%C3%AE-1-smads-and-pi3k-akt-pathways
#8
Liwei Wu, Qinghui Zhang, Wenhui Mo, Jiao Feng, Sainan Li, Jingjing Li, Tong Liu, Shizan Xu, Wenwen Wang, Xiya Lu, Qiang Yu, Kan Chen, Yujing Xia, Jie Lu, Ling Xu, Yingqun Zhou, Xiaoming Fan, Chuanyong Guo
The aim of this study was to investigate the effect of quercetin on hepatic fibrosis, a characteristic response to acute or chronic liver injury. Mice were randomized to bile duct ligation (BDL) or carbon tetrachloride (CCl4) cirrhosis models. Quercetin (100 mg/kg or 200 mg/kg daily) was administered by gavage for 2 or 4 weeks. Liver tissue and blood samples were collected for histological and molecular analysis. The results of our experiments showed that quercetin reduced BDL or CCl4 liver fibrosis, inhibited extracellular matrix formation, and regulated matrix metallopeptidase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810242/mir-490-5p-suppresses-cell-proliferation-and-invasion-by-targeting-bub1-in-hepatocellular-carcinoma-cells
#9
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
#10
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
#11
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
#12
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
#13
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...
November 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-beta-promotes-liver-tumorigenesis-in-mice-via-upregulation-of-snail
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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