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Hepatic stellate cell

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https://www.readbyqxmd.com/read/28110323/aggf1-attenuates-hepatic-inflammation-and-activation-of-hepatic-stellate-cells-by-repressing-ccl2-transcription
#1
Xu Wenping, Zeng Sheng, Li Min, Fan Zhiwen, Zhou Bisheng
Liver injury represents a continuum of pathophysiological processes involving a complex interplay between hepatocytes, macrophages, and hepatic stellate cells. The mechanism whereby these intercellular interactions contribute to liver injury and fibrosis is not completely understood. We report here that angiogenic factor with G patch and FHA domains 1 (Aggf1) was downregulated in the livers of cirrhotic patients compared to healthy controls and in primary hepatocytes in response to carbon tetrachloride (CCl4) stimulation...
October 17, 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28109179/quantitative-and-integrative-analysis-of-paracrine-hepatocyte-activation-by-non-parenchymal-cells-upon-lipopolysaccharide-induction
#2
Katharina Beuke, Frank A Schildberg, Federico Pinna, Ute Albrecht, Roman Liebe, Michaela Bissinger, Peter Schirmacher, Steven Dooley, Johannes G Bode, Percy A Knolle, Ursula Kummer, Kai Breuhahn, Sven Sahle
Gut-derived bacterial lipopolysaccharides (LPS) stimulate the secretion of tumor necrosis factor (TNF) from liver macrophages (MCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs), which control the acute phase response in hepatocytes through activation of the NF-κB pathway. The individual and cooperative impact of non-parenchymal cells on this clinically relevant response has not been analysed in detail due to technical limitations. To gain an integrative view on this complex inter- and intracellular communication, we combined a multi-scale mathematical model with quantitative, time-resolved experimental data of different primary murine liver cell types...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28109152/-hepatic-stellate-cell-conditioned-medium-induces-proliferation-and-epithelial-mesenchymal-transition-via-activating-erk1-2-signaling-pathway-in-hepatoma-cells
#3
Yuxiao Xie, Rui Liao, Long Pan, Kai Fan, Cong Peng, Chengyou Du
Objective To investigate the influence of hepatic stellate cells (HSCs) on malignant biological behavior of hepatoma cells and related mechanisms. Methods Human hepatoma cell lines SMMC-7721 and HepG2, and hepatic stellate cell line LX-2 were cultured separately. HSC conditioned medium (LX2-CM), MAPK specific inhibitor U0126 were used to treat hepatoma cells, separately or together. The invasion and migration abilities of hepatoma cells were detected by Transwell(TM) assay, and cell proliferation was analyzed by CCK-8 assay...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28107589/serum-lincrna-p21-as-a-potential-biomarker-of-liver-fibrosis-in-chronic-hepatitis-b-patients
#4
Fujun Yu, Guangyao Zhou, Kate Huang, XuFei Fan, Guojun Li, Bicheng Chen, Peihong Dong, Jianjian Zheng
Serum long non-coding RNAs (lncRNAs) are emerging as promising biomarkers for various human diseases. The aim of this study was to investigate the feasibility of using serum long intergenic non-coding RNA-p21 (lincRNA-p21) as a biomarker for chronic hepatitis B patients. Serum lincRNA-p21 levels were quantified using real-time PCR in 417 CHB patients and 363 healthy controls. The promoter methylation level of lincRNA-p21 was detected using bisulfite-sequencing analysis in primary hepatic stellate cells (HSCs)...
January 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28106784/microrna-29a-alleviates-bile-duct-ligation-exacerbation-of-hepatic-fibrosis-in-mice-through-epigenetic-control-of-methyltransferases
#5
Ya-Ling Yang, Feng-Sheng Wang, Sung-Chou Li, Mao-Meng Tiao, Ying-Hsien Huang
MicroRNA-29 (miR-29) is found to modulate hepatic stellate cells' (HSCs) activation and, thereby, reduces liver fibrosis pathogenesis. Histone methyltransferase regulation of epigenetic reactions reportedly participates in hepatic fibrosis. This study is undertaken to investigate the miR-29a regulation of the methyltransferase signaling and epigenetic program in hepatic fibrosis progression. miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates were subjected to bile duct-ligation (BDL) to develop cholestatic liver fibrosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28104102/inhibition-of-focal-adhesion-kinase-on-hepatic-stellate-cell-adhesion-and-migration
#6
Yan Wang, Junji Ma, Lei Chen, Xiao-Li Xie, Huiqing Jiang
OBJECTIVE: Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K) signals participate in the activation of HSCs. We evaluated the effect of FAK-related nonkinase (FRNK) on the adhesion and migration of HSCs. MATERIALS AND METHODS: Hepatic fibrosis was induced in Sprague-Dawley rats by means of bile duct ligation. Livers were harvested at 1, 2, 3 and 4 weeks after the ligation; livers of sham-operated animals were harvested at 4 weeks after ligation...
January 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28098912/microrna-9-limits-hepatic-fibrosis-by-suppressing-the-activation-and-proliferation-of-hepatic-stellate-cells-by-directly-targeting-mrp1-abcc1
#7
Jie Sun, Huanying Zhang, Liying Li, Lianfeng Yu, Lifang Fu
Liver fibrosis is a chronic liver disease characterized by the proliferation and activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM). Research suggests that microRNAs (miRNAs) are a new type of regulator of liver fibrosis. In the present study, we investigated the role of microRNA-9 (miR-9) in the process of liver fibrosis, as well as the underlying mechanism of action. Downregulated levels of miR-9 were found in fibrotic liver tissues and activated HSCs as detected by qRT-PCR; whereas, expression of multidrug resistance‑associated protein 1 (MRP1/ABCC1) was upregulated in the fibrotic liver tissues and activated HSCs...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28095789/mirna-338-3p-cdk4-signaling-pathway-suppressed-hepatic-stellate-cell-activation-and-proliferation
#8
Bensong Duan, Jiangfeng Hu, Tongyangzi Zhang, Xu Luo, Yi Zhou, Shun Liu, Liang Zhu, Cheng Wu, Wenxiang Liu, Chao Chen, Hengjun Gao
BACKGROUND: Activated hepatic stellate cell (HSC) is the main fibrogenic cell type in the injured liver. miRNA plays an important role in activation and proliferation of HSC. METHODS: Our previous study examined the expression profiles of microRNAs in quiescent and activated HSC. Real-time PCR and western blot were used to detect the expression of Collagen type I (Col 1) and Alpha-Smooth Muscle Actin (α-SMA). CCK-8 and Edu assay was used to measure the proliferation rate of HSC...
January 17, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28091538/mircorna-145-promotes-activation-of-hepatic-stellate-cells-via-targeting-kr%C3%A3-ppel-like-factor-4
#9
Ruoting Men, Maoyao Wen, Mingyue Zhao, Xuelian Dan, Zongze Yang, Wenchao Wu, Maggie Haitian Wang, Xiaojing Liu, Li Yang
Krüppel-like Factor 4 (KLF4), a target gene of miR-145, can negatively regulate lung fibrosis. However, the potential role of KLF4 and miR-145 in hepatic stellate cells (HSCs) activation or in hepatic fibrosis keeps unclear. This study aims to characterize miR-145 and KLF4 in activated HSCs and liver cirrhotic, and the underlying molecular basis. miR-145 was significantly up-regulated, while KLF4 was dramatically down-regulated during the activation of rat primary HSCs and TGF-βtreated HSCs. Furthermore, miR-145 mimics induced and inhibition of miR-145 reduced α-SMA and COL-I expression in primary HSCs...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090562/hepatitis-c-virus-induced-monocyte-differentiation-into-polarized-m2-macrophages-promotes-stellate-cell-activation-via%C3%A2-tgf-%C3%AE
#10
Banishree Saha, Karen Kodys, Gyongyi Szabo
BACKGROUND & AIMS: Monocyte and macrophage (MΦ) activation contributes to the pathogenesis of chronic hepatitis C virus (HCV) infection. Disease pathogenesis is regulated by both liver-resident MΦs and monocytes recruited as precursors of MΦs into the damaged liver. Monocytes differentiate into M1 (classic/proinflammatory) or M2 (alternative/anti-inflammatory) polarized MΦs in response to tissue microenvironment. We hypothesized that HCV-infected hepatoma cells (infected with Japanese fulminant hepatitis-1 [Huh7...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28078954/nanovesicle-delivery-to-the-liver-via-retinol-binding-protein-and-platelet-derived-growth-factor-receptors-how-targeting-ligands-affect-biodistribution
#11
Ching-Yun Hsu, Chun-Han Chen, Ibrahim A Aljuffali, You-Shan Dai, Jia-You Fang
AIM: Nanovesicles (NVs) conjugating ligands can deliver to the specific nidus. We designed a nanosystem targeting the injectable niosomes to liver for examining biodistribution. METHODOLOGY: Vitamin A and antiplatelet-derived growth factor receptor antibody were employed as the ligands to be taken by hepatic stellate cells. The biodistribution in rats was visualized by bioimaging. RESULTS: A significant liver accumulation was detected for antibody-embedded NVs at 2 h after dosing...
January 12, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28077652/exosome-mediated-intercellular-communication-between-hepatitis-c-virus-infected-hepatocytes-and-hepatic-stellate-cells
#12
Pradip B Devhare, Reina Sasaki, Shubham Shrivastava, Adrian M Di Bisceglie, Ranjit Ray, Ratna B Ray
: Fibrogenic pathways in the liver are principally regulated by activation of hepatic stellate cells (HSC). Fibrosis is associated with chronic hepatitis C virus (HCV) infection, although the mechanism is poorly understood. HSC comprise the major population of the non-parenchymal cells in the liver. Since HCV does not replicate in HSC, we hypothesized that exosomes secreted from HCV-infected hepatocytes activate HSC. Primary or immortalized human hepatic stellate cells (LX2) were exposed to exosomes derived from HCV-infected hepatocytes (HCV-exo) and the expression of fibrosis related genes was examined...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28073161/the-pnpla3-i148m-variant-modulates-the-fibrogenic-phenotype-of-human-hepatic-stellate-cells
#13
Francesca Virginia Bruschi, Thierry Claudel, Matteo Tardelli, Alessandra Caligiuri, Thomas M Stulnig, Fabio Marra, Michael Trauner
: The genetic polymorphism I148M of PNPLA3 is robustly associated with hepatic steatosis and its progression to steatohepatitis, fibrosis and cancer. Hepatic stellate cells (HSCs) are key players in the development of liver fibrosis, but the role of PNPLA3 and its variant I148M in this process is poorly understood. Here we analyzed the expression of PNPLA3 during human HSC activation and thereby explored how a PNPLA3 variant impacts on hepatic fibrogenesis. We show that PNPLA3 gene and protein expression increase during the early phases of activation and remain elevated in fully activated HSCs (p<0...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28068223/hepatocyte-taz-wwtr1-promotes-inflammation-and-fibrosis-in-nonalcoholic-steatohepatitis
#14
Xiaobo Wang, Ze Zheng, Jorge Matias Caviglia, Kathleen E Corey, Tina M Herfel, Bishuang Cai, Ricard Masia, Raymond T Chung, Jay H Lefkowitch, Robert F Schwabe, Ira Tabas
Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease worldwide. However, the molecular basis of how benign steatosis progresses to NASH is incompletely understood, which has limited the identification of therapeutic targets. Here we show that the transcription regulator TAZ (WWTR1) is markedly higher in hepatocytes in human and murine NASH liver than in normal or steatotic liver. Most importantly, silencing of hepatocyte TAZ in murine models of NASH prevented or reversed hepatic inflammation, hepatocyte death, and fibrosis, but not steatosis...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28068221/devilish-effects-of-taz-in-nonalcoholic-steatohepatitis
#15
Scott L Friedman, Youngmin A Lee
Nonalcoholic steatohepatitis leads to cirrhosis and cancer in a rising number of patients with metabolic syndrome. In this issue of Cell Metabolism, Wang et al. (2016) identify the transcriptional co-activator Taz as a driver of inflammation and fibrosis through the induction of Indian hedgehog in hepatocytes, which stimulates fibrogenesis by hepatic stellate cells.
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28067822/pinnisterols-d-j-new-11-acetoxy-9-11-secosterols-with-a-1-4-quinone-moiety-from-formosan-gorgonian-coral-pinnigorgia-sp-gorgoniidae
#16
Yu-Chia Chang, Tsong-Long Hwang, Liang-Mou Kuo, Ping-Jyun Sung
Seven new marine 11-acetoxy-9,11-secosterols, pinnisterols D-J (1-7), with a 1,4-quinone moiety, were discovered from the gorgonian coral Pinnigorgia sp. In this study, the structures of secosterols 1-7 were revealed by spectroscopic analysis. Bioactivity study showed that secosterol 1 treatment inhibited cell viability in a hepatic stellate cell line, HSC-T6, with an IC50 value of 3.93 μM; and secosterols 2, 5, and 7 reduced elastase enzyme release, and 3, 5, and 7 decreased the production of superoxide anions from human neutrophils...
January 6, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28063004/tubulin-alpha-8-is-expressed-in-hepatic-stellate-cells-and-is-induced-in-transformed-hepatocytes
#17
Lisa Rein-Fischboeck, Rebekka Pohl, Elisabeth M Haberl, Sebastian Zimny, Maximilian Neumann, Kristina Eisinger, Thomas S Weiss, Sabrina Krautbauer, Christa Buechler
Tubulin alpha 8 (TUBA8) is highly abundant in murine liver tumors suggesting a role in hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis (NASH) is a risk factor for HCC. In mice that are fed with a methionine-choline deficient diet for two weeks to induce advanced murine NASH, we do see increased hepatic levels of TUBA8 protein. In animals given a high-fat diet for 14 weeks or an atherogenic diet for 12 weeks, hepatic TUBA8 is unchanged. TUBA8 is highly expressed in human hepatic stellate cells (HSC) and co-localizes with the HSC marker desmin in the murine liver...
January 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28061766/chemotherapy-induced-sinusoidal-injury-csi-score-a-novel-histologic-assessment-of-chemotherapy-related-hepatic-sinusoidal-injury-in-patients-with-colorectal-liver-metastasis
#18
Heather L Stevenson, Mariana M Prats, Eizaburo Sasatomi
BACKGROUND: Preoperative neoadjuvant therapy for colorectal liver metastases (CRLM) is increasing in use and can lead to chemotherapy-induced damage to sinusoidal integrity, namely sinusoidal obstruction syndrome (SOS). SOS has been associated with an increased need for intraoperative blood transfusions, increased length of hospitalization post-surgery, decreased tumor response, and a shorter overall survival after resection due to liver insufficiency. It is critical for clinicians and pathologists to be aware of this type of liver injury, and for pathologists to include the status of the background, non-neoplastic liver parenchyma in their pathology reports...
January 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28061416/purinergic-p2x7-receptor-mediates-acetaldehyde-induced-hepatic-stellate-cells-activation-via-pkc-dependent-gsk3%C3%AE-pathway
#19
Xiaojuan Wu, Yuhui Wang, Sheng Wang, Rixiang Xu, Xiongwen Lv
The activation of hepatic stellate cells (HSCs) is an essential part in the development of alcoholic liver fibrosis (ALF). In this study, stimulated HSCs with 200μM acetaldehyde for 48h was used to imitate alcoholic liver fibrosis in vitro. The western blot and qRT-PCR results showed that P2X7R expression was significantly increased in the activation of HSCs after acetaldehyde treatment. Interestingly, activation of P2X7R by stimulating with P2X7R agonist BzATP significantly promoted acetaldehyde-induced CyclinD1 expression, cell proportion in S phase, inflammatory response, and the protein and mRNA levels of α-SMA, collagen I...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28052321/canonical-hedgehog-signaling-regulates-hepatic-stellate-cell-mediated-angiogenesis-in-liver-fibrosis
#20
Feng Zhang, Meng Hao, Huanhuan Jin, Zhen Yao, Naqi Lian, Li Wu, Jiangjuan Shao, Anping Chen, Shizhong Zheng
BACKGROUND AND PURPOSE: Hepatic stellate cells (HSCs) are liver-specific pericytes regulating angiogenesis during liver fibrosis. We aimed to elucidate the mechanisms by which hedgehog signaling regulated HSC angiogenic properties and to validate the therapeutic implications. EXPERIMENTAL APPROACH: Rats and mice were intoxicated with carbon tetrachloride for in vivo evaluation of hepatic angiogenesis and fibrotic injury. Diversified molecular approaches including real-time PCR, Western blot, luciferase reporter assay, chromatin immunoprecipitation, electrophoretic mobility shift assay, and co-immunoprecipitation were used to investigate the underlying mechanisms in vitro...
January 4, 2017: British Journal of Pharmacology
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