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Hepatic stellate cells

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https://www.readbyqxmd.com/read/28929107/microrna-195-activates-hepatic-stellate-cells-in-vitro-by-targeting-smad7
#1
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/28927250/gut-microbiota-and-the-liver
#2
Alessandro Federico, Marcello Dallio, Giuseppe G Caprio, Vittorio M Ormando, Carmela Loguercio
Nowadays liver diseases represent one of major healthy problems in the world in terms of morbidity and mortality. The high prevalence of liver pathologies represents the key point to understand the necessity to identify the pathogenetic mechanisms that support these disorders in order to nurse them. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Gut microbiota is considered both as a promoting factor and as a potential therapeutic target of a large number of liver pathologies due to the connection between intestine and liver: the gut-liver axis...
December 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28919365/hepatic-stellate-cell-specific-deletion-of-sirt1-exacerbates-liver-fibrosis-in-mice
#3
Min Li, Wenxuan Hong, Chenzhi Hao, Luyang Li, Huihui Xu, Ping Li, Yong Xu
Liver fibrosis is widely perceived as a host defense mechanism that aids tissue repair following liver injury. Excessive fibrogenesis, however, serves to disrupts normal liver structure and precedes such irrevocable human pathologies as cirrhosis and hepatocellular carcinoma. Activation of hepatic stellate cells (HSCs) is a hallmark event during liver fibrosis. In the present study we investigated the mechanism by which the lysine deacetylase SIRT1 regulates HSC activation. We report here that SIRT1 levels were decreased in the liver in different mouse models and in cultured HSCs undergoing activation...
September 14, 2017: Biochimica et Biophysica Acta
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
#4
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/28917627/molecular-and-functional-characterization-of-cd133-stem-progenitor-cells-infused-in-patients-with-end-stage-liver-disease-reveals-their-interplay-with-stromal-liver-cells
#5
Lucia Catani, Daria Sollazzo, Elisa Bianchi, Marilena Ciciarello, Chiara Antoniani, Licia Foscoli, Paolo Caraceni, Ferdinando Antonino Giannone, Maurizio Baldassarre, Rosaria Giordano, Tiziana Montemurro, Elisa Montelatici, Antonia D'Errico, Pietro Andreone, Valeria Giudice, Antonio Curti, Rossella Manfredini, Roberto Massimo Lemoli
BACKGROUND AIMS: Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133(+) stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. METHODS: Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133(+) cell therapy...
September 13, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28916723/fibroblast-growth-factor-2-fgf2-regulates-cytoglobin-expression-and-activation-of-human-hepatic-stellate-cells-via-jnk-signaling
#6
Misako Sato-Matsubara, Tsutomu Matsubara, Atsuko Daikoku, Yoshinori Okina, Lisa Longato, Krista Rombouts, Le Thi Thanh Thuy, Jun Adachi, Takeshi Tomonaga, Kazuo Ikeda, Katsutoshi Yoshizato, Massimo Pinzani, Norifumi Kawada
Cytoglobin (CYGB) belongs to the mammalian globin family and is exclusively expressed in hepatic stellate cells (HSCs) in the liver. In addition to its gas-binding ability, CYGB is relevant to hepatic inflammation, fibrosis, and cancer because of its antioxidative properties; however, the regulation of CYGB gene expression remains unknown. Here, we sought to identify factors that induce CYGB expression in HSCs and to clarify the molecular mechanism involved. We used the human HSC cell line HHSteC and primary human HSCs isolated from intact human liver tissues...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915589/casticin-attenuates-liver-fibrosis-and-hepatic-stellate-cell-activation-by-blocking-tgf-%C3%AE-smad-signaling-pathway
#7
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/28903404/tumor-specific-hepatic-stellate-cells-thscs-induces-digr2-expression-in-dendritic-cells-to-inhibit-t-cells
#8
Yun-Hong Xia, Zhen Lu, Min Zhao, Wen-Ting Dai, Lu Ding, Li-Xia Hu, Guo-Lin Jiang
Tumor-specific hepatic stellate cells (tHSCs) contributes to tumorigenesis and progression of hepatocellular carcinoma (HCC). The potential function of tHSCs on dendritic cells (DCs) was studied here. We discovered that tHSCs co-culture induced upregulation of DIgR2 (dendritic cell-derived immunoglobulin receptor 2) in bone marrow-derived DCs (mDCs). Activation of MEK-ERK is required for DIgR2 expression in mDCs. MEK-ERK inhibitors or shRNA-mediated silence of MEK1/2 in mDCs inhibited tHSCs-induced DIgR2 expression...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903397/dlgr2-knockdown-boosts-dendritic-cell-activity-and-inhibits-hepatocellular-carcinoma-tumor-in-situ-growth
#9
Zhen Lu, Yun-Hong Xia, Min Zhao, Bing Zhang, Wen-Ting Dai, Lu Ding, Li-Xia Hu, Jin-Ling Bi, Guo-Lin Jiang
Tumor-specific hepatic stellate cells (tHSCs) positively participate in human hepatocellular carcinoma (HCC) tumorigenesis and progression. Our previous studies have shown that tHSCs co-culture with dendritic cells (DCs) induced DIgR2 (dendritic cell-derived immunoglobulin receptor 2) expression. The latter is a member of IgSF inhibitory receptor suppressing DCs-initiated antigen-specific T-cell responses. In the current study, we show that hepatic artery injection of DlgR2 siRNA significantly inhibited in-situ HCC xenograft growth in rat livers...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902846/downregulation-of-microrna-145-may-contribute-to-liver-fibrosis-in-biliary-atresia-by-targeting-add3
#10
Yongqin Ye, Zhihan Li, Qi Feng, Zimin Chen, Zhouguang Wu, Jianyao Wang, Xiaoshuo Ye, Dahao Zhang, Lei Liu, Wei Gao, Lihui Zhang, Bin Wang
BACKGROUND AND OBJECTIVES: Biliary atresia (BA) is a pediatric liver disease characterized by fibro-obliteration and obstruction of the extrahepatic biliary system, that invariably leads to cirrhosis and even death, if left untreated for extended time. However, its pathology and etiology still remained unknown. In this study, we tested the expression of adducin 3 (ADD3), the gene identified as a susceptibility gene in BA by GWAS, and uncovered its upstream regulatory microRNA in the pathogenesis of BA...
2017: PloS One
https://www.readbyqxmd.com/read/28902784/pancreatic-stellate-cells-have-distinct-characteristics-from-hepatic-stellate-cells-and-are-not-the-unique-origin-of-collagen-producing-cells-in-the-pancreas
#11
Gen Yamamoto, Kojiro Taura, Keiko Iwaisako, Masataka Asagiri, Shinji Ito, Yukinori Koyama, Kazutaka Tanabe, Kohta Iguchi, Motohiko Satoh, Takahiro Nishio, Yukihiro Okuda, Yoshinobu Ikeno, Kenji Yoshino, Satoru Seo, Etsuro Hatano, Shinji Uemoto
OBJECTIVES: The origin of collagen-producing myofibroblasts in pancreatic fibrosis is still controversial. Pancreatic stellate cells (PSCs), which have been recognized as the pancreatic counterparts of hepatic stellate cells (HSCs), are thought to play an important role in the development of pancreatic fibrosis. However, sources of myofibroblasts other than PSCs may exist because extensive studies of liver fibrosis have uncovered myofibroblasts that did not originate from HSCs. This study aimed to characterize myofibroblasts in an experimental pancreatic fibrosis model in mice...
October 2017: Pancreas
https://www.readbyqxmd.com/read/28901425/knockdown-of-fstl1-attenuates-hepatic-stellate-cell-activation-through-the-tgf%C3%A2-%C3%AE-1-smad3-signaling-pathway
#12
Hongye Shang, Xiangjin Liu, Hui Guo
Follistatin‑like 1 (Fstl1) is a secreted glycoprotein that belongs to the follistatin and SPARC (secreted protein, acidic and rich in cysteine) families and was identified to serve a critical role in lung fibrosis. However, the role of Fstl1 in liver fibrosis remains undefined. Therefore, the aim of the present study was to investigate the role of Fstl1 in liver fibrosis. The results indicated that Fstl1 was highly expressed in human hepatic fibrosis tissues and activated hepatic stellate cells (HSCs). Furthermore, knockdown of Fstl1effectively suppressed HSC proliferation and the protein expression levels of α‑SMA and collagen I in transforming growth factor (TGF)‑β1‑treated HSCs...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28898276/liver-myofibroblasts-of-murine-origins-express-mesothelin-identification-of-novel-rat-mesothelin-splice-variants
#13
Michel Fausther, Elise G Lavoie, Jonathan A Dranoff
Liver myofibroblasts are specialized effector cells that drive hepatic fibrosis, a hallmark process of chronic liver diseases, leading to progressive scar formation and organ failure. Liver myofibroblasts are increasingly recognized as heterogeneous with regards to their origin, phenotype, and functions. For instance, liver myofibroblasts express cell markers that are universally represented such as, ItgαV and Pdgfrβ, or restricted to a given subpopulation such as, Lrat exclusively expressed in hepatic stellate cells, and Gpm6a in mesothelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28895372/-tipping-extracellular-matrix-remodelling-towards-regression-of-liver-fibrosis-novel-concepts
#14
Fernando Magdaleno, Robert Schierwagen, Frank E Uschner, Jonel Trebicka
Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, as well as other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC)...
September 11, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28890699/sphingosine-1-phosphate-signaling-as-a-target-in-hepatic-fibrosis-therapy
#15
REVIEW
Bárbara González-Fernández, Diana I Sánchez, Javier González-Gallego, María J Tuñón
Liver fibrosis is an excess production of extracellular matrix proteins as a result of chronic liver disease which leads to cell death and organ dysfunction. The key cells involved in fibrogenesis are resident hepatic stellate cells (HSCs) which are termed myofibroblasts after activation, acquiring contractile, proliferative, migratory and secretory capability. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with well-established effects on angiogenesis, carcinogenesis and immunity. Accumulating evidence demonstrates that this metabolite is involved in the profibrotic inflammatory process through the regulation of pleiotropic cell responses, such as vascular permeability, leukocyte infiltration, cell survival, migration, proliferation and HSCs differentiation to myofibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28890106/development-of-a-peptide-modified-sirna-nanocomplex-for-hepatic-stellate-cells
#16
Zhen Zhao, Yuanke Li, Akshay Jain, Zhijin Chen, Hao Liu, Wei Jin, Kun Cheng
Insulin-like growth factor 2 receptor (IGF2R) is overexpressed in activated hepatic stellate cells (HSCs) and therefore can be utilized for HSC-specific drug delivery. We recently discovered an IGF2R-specific peptide using a novel biopanning. Here, we adopted biotin-conjugated IGF2R-specific peptide, cholesterol, and vitamin A as the targeting ligands for the neutravidin-based siRNA nanocomplex to deliver PCBP2 siRNA, a potentially antifibrotic agent, to HSCs. Compared to vitamin A and cholesterol, the IGF2R-specific peptide exhibited the highest targeting effect to human LX-2 HSC, rat HSC-T6 cell line, and activated primary rat HSCs...
September 7, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28887481/glycosylation-dependent-galectin-1-neuropilin-1-interactions-promote-liver-fibrosis-through-activation-of-tgf-%C3%AE-and-pdgf-like-signals-in-hepatic-stellate-cells
#17
Ming-Heng Wu, Yuh-Ling Chen, Kuen-Haur Lee, Che-Chang Chang, Tsai-Mu Cheng, Szu-Yuan Wu, Chao-Chiang Tu, Wan-Lin Tsui
Concomitant expressions of glycan-binding proteins and their bound glycans regulate many pathophysiologic processes, but this issue has not been addressed in liver fibrosis. Activation of hepatic stellate cells (HSCs) is a rate-limiting step in liver fibrosis and is an important target for liver fibrosis therapy. We previously reported that galectin (Gal)-1, a β-galactoside-binding protein, regulates myofibroblast homeostasis in oral carcinoma and wound healing, but the role of Gal-1 in HSC migration and activation is unclear...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28885731/a-multifunctional-nanocarrier-for-efficient-trail-based-gene-therapy-against-hepatocellular-carcinoma-with-desmoplasia
#18
Chun-Hung Liu, Guann-Gen Chern, Fu-Fei Hsu, Kuan-Wei Huang, Yun-Chieh Sung, Hsi-Chien Huang, Jiantai Timothy Qiu, Sheng-Kai Wang, Chu-Chi Lin, Chien-Hsun Wu, Han-Chung Wu, Jia-Yu Liu, Yunching Chen
The anti-cancer efficacy of TNF-related apoptosis-inducing ligand (TRAIL)-based therapy is limited due to systemic toxicity, poor bioavailability, and the development of TRAIL-resistance. We developed a tumor-targeted LCPP (Lipid/Calcium/Phosphate/Protamine) nanoparticle (NP) to deliver TRAIL plasmid DNA (pDNA) into hepatocellular carcinoma (HCC) cells. TRAIL pDNA was encapsulated in a pH stimuli-responsive calcium phosphate (CaP) core, and protamine was added to facilitate nuclear delivery of pDNA. In addition, the intracellular release of Ca(2+) from the CaP core overcame TRAIL resistance via calcium influx-dependent DR5 upregulation...
September 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28884481/estrogen-receptor-%C3%AE-selective-agonist-ameliorates-liver-cirrhosis-in-rats-by-inhibiting-the-activation-and-proliferation-of-hepatic-stellate-cells
#19
Bin Zhang, Cheng-Gang Zhang, Lin-Hua Ji, Gang Zhao, Zhi-Yong Wu
AIM: To explore the roles of ER subtypes and corresponding agonists/antagonists on the development of cirrhosis and activation and proliferation of HSCs. METHODS: Carbon tetrachloride (CCl4 ) -induced cirrhotic ovariectomized rats were administered non-selective ER agonist (β-estradiol, E2), ER selective agonists (ERα agonist, PPT; ERβ agonist, DPN; GPER agonist, G1) or E2 + ER selective antagonists (ERα antagonist, MPP; ERβ antagonist, PHTPP; GPER antagonist, G15) for 12 weeks...
September 7, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28883696/metabolomic-profiling-for-identification-of-metabolites-and-relevant-pathways-for-taurine-in-hepatic-stellate-cells
#20
Xin Deng, Xing-Qiu Liang, Fei-Guo Lu, Xiao-Fang Zhao, Lei Fu, Jian Liang
AIM: To develop a reliable and simple method to identify important biological metabolites and relevant pathways for taurine in hepatic stellate cells (HSCs), in order to provide more data for taurine therapy. METHODS: All the biological samples were analyzed by using high-performance liquid chromatography-time electrospray ionization/quadrupole-time of flight mass spectrometry. Principal component analysis and partial least squares discriminant analysis were used to identify statistically different metabolites for taurine in HSCs, and metabolomic pathway analysis was used to do pathway analysis for taurine in HSCs...
August 21, 2017: World Journal of Gastroenterology: WJG
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