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Hepatic stellate cells

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https://www.readbyqxmd.com/read/27917262/toll-like-receptors-in-pathophysiology-of-liver-diseases
#1
REVIEW
Safak Kiziltas
Toll-like receptors (TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated molecular patterns. Given constant exposure to pathogens from gut, strict control of TLR-associated signaling pathways is essential in the liver, which otherwise may lead to inappropriate production of pro-inflammatory cytokines and interferons and may generate a predisposition to several autoimmune and chronic inflammatory diseases...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27915160/histone-deacetylase-9-plays-a-role-in-the-antifibrogenic-effect-of-astaxanthin-in-hepatic-stellate-cells
#2
Yue Yang, Minkyung Bae, Young-Ki Park, Yoojin Lee, Tho X Pham, Swetha Rudraiah, José Manautou, Sung I Koo, Ji-Young Lee
Activation of hepatic stellate cells (HSCs) is critical for liver fibrosis development. Previously, we showed that astaxanthin (ASTX), a xanthophyll carotenoid, has antifibrogenic effects in LX-2 cells, a human HSC cell line. We sought to determine the effect of ASTX on HSC activation, and to identify molecular mediators that are critically involved in the processes. ASTX prevented the activation of mouse primary HSCs, as evidenced by attenuated induction of procollagen type I α1. In human primary HSCs, ASTX also inhibited transforming growth factor β1 (TGFβ1)-induced fibrogenic gene expression...
November 12, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27907201/tumor-necrosis-factor-like-weak-inducer-of-apoptosis-promotes-hepatic-stellate-cells-migration-via-canonical-nf-%C3%AE%C2%BAb-mmp9-pathway
#3
Mingcui Xu, Feng Zhang, Aixiu Wang, Chen Wang, Yu Cao, Ming Zhang, Mingming Zhang, Min Su, Xiaoping Zou, Guifang Xu, Yuzheng Zhuge
In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) have mainly been assessed in association with liver regeneration. However, the effects of TWEAK on liver fibrosis have not been fully elucidated. To investigate the effects of TWEAK on human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms, human HSCs line-LX-2 were cultured with TWEAK. Cell migration was detected by transwell assay; cell viability was evaluated by Cell Counting Kit-8; the expression of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 gene was identified by quantitative real-time polymerase chain reaction and western blotting; the activity of matrix metalloproteinases (MMPs) was tested by enzyme-linked immuno sorbent assay; small interfering RNA transfection was applied for depletion of MMP9 and p65...
2016: PloS One
https://www.readbyqxmd.com/read/27899232/expression-of-muscarinic-acetylcholine-receptors-in-hepatocytes-from-rat-fibrotic-liver
#4
Lin Luo, Tingting Xu, Pengbo Wang, Liuliu Mao, Chenghao Xi, Jinhua Huang, Wei Zhang
The pathological changes of parasympathetic nerve are considered as an independent prognostic factor of the survival rate of patients with chronic liver disease. The non-selective muscarinic acetylcholine receptors (mAchR) agonists and antagonists can affect the proliferation of hepatocytes and hepatic stellate cells, but the subtypes of mAchR expressions in HCs are still uncertain. Here, we investigate the expression of mAchR in hepatic fibrosis on rats. 3ml/kg 40% carbon tetrachloride (CCL4) was given to induce hepatic fibrosis on rats and the hepatocytes were isolated...
November 26, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27896916/dihydroartemisinin-counteracts-fibrotic-portal-hypertension-via-farnesoid-x-receptor-dependent-inhibition-of-hepatic-stellate-cell-contraction
#5
Wenxuan Xu, Chunfeng Lu, Feng Zhang, Jiangjuan Shao, Shunyu Yao, Shizhong Zheng
Portal hypertension is a frequent pathological symptom occurring especially in hepatic fibrosis and cirrhosis. Current paradigms indicate that inhibition of hepatic stellate cell (HSC) activation and contraction is anticipated to be an attractive therapeutic strategy, because activated HSC dominantly facilitates an increase in intrahepatic vein pressure through secreting extracellular matrix and contracting. Our previous in vitro study indicated that dihydroartemisinin (DHA) inhibited contractility of cultured HSC by activating intracellular farnesoid X receptor (FXR)...
November 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27895415/factoring-the-intestinal-microbiome-into-the-pathogenesis-of-autoimmune-hepatitis
#6
EDITORIAL
Albert J Czaja
The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora (dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria...
November 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27894668/txn1-ctsd-and-cdk4-are-key-proteins-of-combination-therapy-with-taurine-epigallocatechin-gallate-and-genistein-against-liver-fibrosis-in-rats
#7
Wen Cao, Yan Li, Min Li, Xuerong Zhang, Ming Liao
The anti-fibrotic mechanism of combination therapy with taurine, epigallocatechin gallate and genistein was studied from the perspective of serum proteomics in our previous work. In order to further investigate and systematically analyse other possible therapeutic mechanism of combination therapy against liver fibrosis, isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis was applied to study the protein profile changes in liver tissue of carbon tetrachloride-induced liver fibrosis rats after combination therapy...
November 25, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27890721/reactive-gamma-ketoaldehydes-as-novel-activators-of-hepatic-stellate-cells-in-vitro
#8
Lisa Longato, Fausto Andreola, Sean S Davies, Jackson L Roberts, Giuseppe Fusai, Massimo Pinzani, Kevin Moore, Krista Rombouts
AIMS: Products of lipid oxidation, such as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSC) to a pro-fibrogenic phenotype. Isolevuglandins (IsoLG) are a family of acyclic γ-ketoaldehydes formed through oxidation of arachidonic acid or as by-products of the cyclooxygenase pathway. IsoLGs are highly reactive aldehydes which are efficient at forming protein adducts and cross-links at concentrations 100-fold lower than 4-hydroxynonenal. Since the contribution of IsoLGs to liver injury has not been studied, we synthesized 15-E2-IsoLG and used it to investigate whether IsoLG could induce activation of HSC...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890429/knockdown-of-hipk2-attenuates-the-pro-fibrogenic-response-of-hepatic-stellate-cells-induced-by-tgf-%C3%AE-1
#9
Ping He, Zu-Jiang Yu, Chang-Yu Sun, Shu-Jie Jiao, He-Qing Jiang
Homeodomain-interacting protein kinase 2 (HIPK2), a member of HIPKs family, is considered as a key regulator in fibrosis. However, the roles of HIPK2 in hepatic stellate cells (HSCs) activation and liver fibrosis are still unclear. Therefore, in this study, we investigated the roles of HIPK2 in HSCs activation and liver fibrosis. Our results showed that HIPK2 expression was significantly up-regulated in liver fibrotic tissues and TGF-β1-treated HSCs. Knockdown of HIPK2 significantly inhibited TGF-β1-induced HSCs proliferation, as well as decreased the expression levels of α-SMA and collagen I...
November 24, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27888541/tweak-increases-sirt1-expression-and-promotes-p53-deacetylation-affecting-human-hepatic-stellate-cell-senescence
#10
Feng Zhang, Ming Zhang, Aixiu Wang, Mingcui Xu, Chen Wang, Guifang Xu, Bin Zhang, Xiaoping Zou, Yuzheng Zhuge
To detect the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) on SIRT1 expression and p53 deacetylation, involving cell senescence, in activated human hepatic stellate cell (HSC) in vitro, human HSC LX-2 was cultured with TWEAK for 24 h. The result showed that the expression of membrane receptor Fn14 was remarkably increased by TWEAK, which up regulated SIRT1 in LX-2 cells, detecting by western blotting and real-time PCR. The expression of p53 was not significantly altered; however, the ac-p53 was decreased...
November 26, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27886086/ligustrazine-oleanolic-acid-glycine-derivative-g-toa-selectively-inhibited-the-proliferation-and-induced-apoptosis-of-activated-hsc-t6-cells
#11
Siling Bi, Fuhao Chu, Mina Wang, Bi Li, Pei Mao, Huazheng Zhang, Penglong Wang, Wenbo Guo, Liang Xu, Liwei Ren, Haimin Lei, Yuzhong Zhang
Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA)...
November 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27885847/receptor-specific-trail-as-a-means-to-achieve-targeted-elimination-of-activated
#12
Mohammad Arabpour, Robbert Cool, Klaas Nico Faber, Wim J Quax, Hidde J Haisma
Activated Hepatic Stellate Cells (HSCs) are known to play a central role in liver fibrosis and their elimination is a crucial step towards the resolution and reversion of liver fibrosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a molecule that may contribute to the apoptotic removal of activated HSC through binding to its dedicated receptors. In the present study, we investigated the potential application of recombinant receptor-specific TRAIL proteins in the efficient elimination of activated HSCs...
November 25, 2016: Journal of Drug Targeting
https://www.readbyqxmd.com/read/27883059/hepatic-satb1-induces-paracrine-activation-of-hepatic-stellate-cells-and-is-upregulated-by-hbx
#13
Jin Gong, Wei Tu, Jian Han, Jiayi He, Jingmei Liu, Ping Han, Yunwu Wang, Mengke Li, Mei Liu, Jiazhi Liao, Dean Tian
Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, but its involvement in hepatic fibrogenesis remains unclear. Special AT-rich binding protein 1 (SATB1) has been implicated in reprogramming chromatin organization and transcription profiles in many cancers and non-cancer-related conditions. We found that hepatic SATB1 expression was significantly up-regulated in fibrotic tissues from chronic hepatitis B virus (HBV)-infected patients and HBV transgenic (HBV-Tg) mouse model...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882166/galanin-receptor-2-mediates-antifibrogenic-effects-of-galanin-on-hepatic-stellate-cells
#14
Lingnan He, Zhenghong Li, Da Zhou, Yongnian Ding, Leiming Xu, Yuanwen Chen, Jiangao Fan
Galanin is an endogenous factor involved in the negative regulation of the biological effects of leptin in bioenergetic metabolism. Leptin promotes fibrogenic effects in hepatic stellate cells (HSCs), however, little is known about the effects of galanin on HSCs. In the present study, the biological functions of galanin and its receptors (GalRs) in HSCs were investigated using cell culture in vitro. It was found that galanin and GalR3 mRNA are expressed in quiescent and activated HSCs. GalR2 expression was undetectable in quiescent HSCs but was markedly induced in activated HSCs...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27881436/knockdown-of-histidine-rich-calcium-binding-protein-hrc-suppresses-liver-fibrosis-by-inhibiting-the-activation-of-hepatic-stellate-cells
#15
Jingmei Liu, Mengke Li, Jin Gong, Ping Han, Yunwu Wang, Dean Tian, Jiazhi Liao
The histidine-rich calcium binding protein (HRC) is a regulator of Ca(2+)- homeostasis and it plays a significant role in hepatocellular carcinoma (HCC) progression. However, the relationship between HRC and liver fibrogenesis is still unknown. Our data demonstrated that HRC was upregulated in fibrotic liver and activated HSCs. TGF-β treatment increased α-SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced α-SMA, CTGF and collagens expression, and inhibited HSCs proliferation and migration...
November 23, 2016: Biology Open
https://www.readbyqxmd.com/read/27878234/prometastatic-mechanisms-of-caf-mediated-emt-regulation-in-pancreatic-cancer-cells
#16
Tao Shan, Shuo Chen, Xi Chen, Wan Run Lin, Wei Li, Jiancang Ma, Tao Wu, Hong Ji, Yiming Li, Xijuan Cui, Ya'an Kang
Tumor metastasis are accompanied by the EMT (epithelial-mesenchymal transition)-MET (mesenchymal-epithelial transition) two-step process. In this study, we investigated the importance of cancer associated fibroblasts (CAF) in the process. First, the primary cultures of isolated pancreatic CAF, fibroblasts of normal pancreatic tissues (NF), and normal hepatic stellate cells (HSF) were identified and verified via the expression of α-SMA and vimentin. Using an indirect three-dimensional co-culture model, the morphological changes were observed by light microscopy and laser scanning confocal microscopy...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27876602/genistein-attenuates-d-galn-induced-liver-fibrosis-chronic-liver-damage-in-rats-by-blocking-the-tgf-%C3%AE-smad-signaling-pathways
#17
Ajaz Ahmad Ganai, Mohammad Husain
BACKGROUND AND AIM: Genistein is a major isoflavonoid abundantly found in soy. Earlier genistein has been reported to possess protective effect against a multitude of disorders including cancer. Previously we demonstrated the protective effects of Genistein in d-Galactosamine (D-GalN) induced fulminant hepatic failure (FHF) in rats. In present study, we evaluated the hepatoprotective activity of Genistein in rat model of chronic liver damage and liver fibrosis. METHODS: Liver fibrosis was induced by intraperitoneal injection of D-GalN (250 mg/kg BW) twice a week for 12 weeks...
November 19, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27876093/involvement-of-hepatic-macrophages-in-the-antifibrotic-effect-of-igf-i-overexpressing-mesenchymal-stromal-cells
#18
Esteban Fiore, Mariana Malvicini, Juan Bayo, Estanislao Peixoto, Catalina Atorrasagasti, Romina Sierra, Marcelo Rodríguez, Sofia Gómez Bustillo, Mariana G García, Jorge B Aquino, Guillermo Mazzolini
BACKGROUND: Cirrhosis is a major health problem worldwide and new therapies are needed. Hepatic macrophages (hMø) have a pivotal role in liver fibrosis, being able to act in both its promotion and its resolution. It is well-known that mesenchymal stromal cells (MSCs) can modulate the immune/inflammatory cells. However, the effects of MSCs over hMø in the context of liver fibrosis remain unclear. We previously described evidence of the antifibrotic effects of in vivo applying MSCs, which were enhanced by forced overexpression of insulin-like growth factor 1 (AdIGF-I-MSCs)...
November 22, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27872616/novel-approach-for-evaluation-of-bacteroides-fragilis-protective-role-against-bartonella-henselae-liver-damage-in-immunocompromised-murine-model
#19
Chiara Pagliuca, Annunziata G Cicatiello, Roberta Colicchio, Adelaide Greco, Raimondo Cerciello, Luigi Auletta, Sandra Albanese, Elena Scaglione, Caterina Pagliarulo, Gabiria Pastore, Gelsomina Mansueto, Arturo Brunetti, Bice Avallone, Paola Salvatore
Bartonella henselae is a gram-negative facultative intracellular bacterium and is the causative agent of cat-scratch disease. Our previous data have established that Bacteroides fragilis colonization is able to prevent B. henselae damages through the polysaccharide A (PSA) in an experimental murine model. In order to determine whether the PSA is essential for the protection against pathogenic effects of B. henselae in immunocompromised hosts, SCID mice were co-infected with B. fragilis wild type or its mutant B...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27872076/anti-schistosomiasis-liver-fibrosis-effects-of-chlorogenic-acid-through-il-13-mir-21-smad7-signaling-interactions-in-vivo-and-in-vitro
#20
Yao Wang, Fan Yang, Jun Xue, Xuan Zhou, Lei Luo, Qian Ma, Yun-Fei Chen, Juan Zhang, Shu-Ling Zhang, Lei Zhao
This study is to investigate the anti-Schistosomiasis liver fibrosis effects of chlorogenic acid (CGA) on IL-13/miR-21/Smad7 signaling interactions in hepatic stellate LX2 cell line and Schistosome-infected mice. The transfection was based on the GV273-miR-21-EGFP and GV369-miR-21-EGFP lentiviral system to up- or down-regulate miR-21 gene in LX2 cells. The mRNA expression of miR-21, Smad7 and connective tissue growth factor (CTGF) and protein expression of Smad7, CTGF, Smad1, p-Smad1, Smad2, p-Smad2, Smad2/3, p-Smad2/3, TGF-β receptor I and α-SMA were assayed...
November 21, 2016: Antimicrobial Agents and Chemotherapy
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