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Hepatic stellate cells

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https://www.readbyqxmd.com/read/28739486/microrna-146a-5p-attenuates-liver-fibrosis-by-suppressing-profibrogenic-effects-of-tgf%C3%AE-1-and-lipopolysaccharide
#1
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/28737764/paired-related-homeobox-protein-1-regulates-pdgf-induced-chemotaxis-of-hepatic-stellate-cells-in-liver-fibrosis
#2
Jin Gong, Jian Han, Jiayi He, Jingmei Liu, Ping Han, Yunwu Wang, Mengke Li, Dongxiao Li, Xiangming Ding, Zhipeng Du, Jiazhi Liao, Dean Tian
Activation of the platelet-derived growth factor (PDGF)/PDGF beta receptor (PDGFβR) axis has a critical role in liver fibrosis. However, the mechanisms that regulate the PDGF signaling are yet to be elucidated. The present study demonstrates that paired related homeobox protein 1 (Prrx1) is involved in PDGF-dependent hepatic stellate cell (HSCs) migration via modulation of the expression of metalloproteinases MMP2 and MMP9. PDGF elevated the level of Prrx1 through the activation of ERK/Sp1 and PI3K/Akt/Ets1 pathways...
July 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28734947/platelet-derived-growth-factor-receptor-alpha-contributes-to-human-hepatic-stellate-cell-proliferation-and-migration
#3
Alexander Kikuchi, Tirthadipa Pradhan-Sundd, Sucha Singh, Shanmugam Nagarajan, Nick Loizos, Satdarshan Monga
Platelet-derived growth factor receptor alpha (PDGFRα), a tyrosine kinase receptor, is up-regulated in hepatic stellate cells (HSCs) during chronic liver injury. HSCs mediate hepatic fibrosis through their activation from a quiescent state partially in response to pro-fibrotic growth factors. HSC activation entails enhanced expression of pro-fibrotic genes, increase in proliferation, and increase in motility, which facilitates migration within the hepatic lobule. We show co-localization of PDGFRα in murine carbon tetrachloride, bile duct ligation (BDL), and 0...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28731181/mir%C3%A2-21-promotes-%C3%AE-%C3%A2-sma-and-collagen-i-expression-in-hepatic-stellate-cells-via-the-smad7-signaling-pathway
#4
Rong-Quan Fu, Dan-Ping Hu, Yi-Bing Hu, Liang Hong, Qing-Feng Sun, Ji-Guang Ding
The aim of the present study was to investigate the role of microRNA (miR)‑21 in regulating collagen I and Smad7 expression in activated rat hepatic stellate cells (HSCs). Rat HSCs were isolated by single‑step density gradient centrifugation with Nycodenz. Cellular content of miR‑21, SMAD7, α‑smooth muscle actin (α‑SMA), collagen type I alpha 1 (COLLA1) and COLL alpha 2 (A2) mRNA was examined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and cellular content of Smad7 and α‑SMA protein was detected by western blotting...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28731149/the-role-of-t-helper-17-cells-in-the-pathogenesis-of-hepatitis-b-virus-related-liver-cirrhosis-review
#5
Suxia Bao, Jianming Zheng, Guangfeng Shi
In chronic hepatitis B virus (HBV)-infected patients, T helper 17 (Th17) cells are significantly elevated. Th17 cells initiate immune‑mediated pathogenesis and have a critical role in the process of HBV‑related liver cirrhosis (HBV‑LC). The mechanisms underlying this process are attributed to Th17‑secreted cytokines, which include interleukin (IL)‑17, IL‑21 and IL‑22; however, a systemic analysis regarding these mechanisms has yet to be conducted. Therefore, the present study aimed to investigate the role of Th17 cells in the pathogenesis of HBV‑LC...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28717244/trail-regulatory-receptors-constrain-human-hepatic-stellate-cell-apoptosis
#6
Harsimran D Singh, Itziar Otano, Krista Rombouts, Kasha P Singh, Dimitra Peppa, Upkar S Gill, Katrin Böttcher, Patrick T F Kennedy, Jude Oben, Massimo Pinzani, Henning Walczak, Giuseppe Fusai, William M C Rosenberg, Mala K Maini
The TRAIL pathway can mediate apoptosis of hepatic stellate cells to promote the resolution of liver fibrosis. However, TRAIL has the capacity to bind to regulatory receptors in addition to death-inducing receptors; their differential roles in liver fibrosis have not been investigated. Here we have dissected the contribution of regulatory TRAIL receptors to apoptosis resistance in primary human hepatic stellate cells (hHSC). hHSC isolated from healthy margins of liver resections from different donors expressed variable levels of TRAIL-R2/3/4 (but negligible TRAIL-R1) ex vivo and after activation...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717194/rapid-production-of-human-liver-scaffolds-for-functional-tissue-engineering-by-high-shear-stress-oscillation-decellularization
#7
Giuseppe Mazza, Walid Al-Akkad, Andrea Telese, Lisa Longato, Luca Urbani, Benjamin Robinson, Andrew Hall, Kenny Kong, Luca Frenguelli, Giusi Marrone, Oliver Willacy, Mohsen Shaeri, Alan Burns, Massimo Malago, Janet Gilbertson, Nigel Rendell, Kevin Moore, David Hughes, Ioan Notingher, Gavin Jell, Armando Del Rio Hernandez, Paolo De Coppi, Krista Rombouts, Massimo Pinzani
The development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of human acellular liver tissue cubes (ALTCs) using normal liver tissue unsuitable for transplantation. The application of high shear stress is a key methodological determinant accelerating the process of tissue decellularization while maintaining ECM protein composition, 3D-architecture and physico-chemical properties of the native tissue...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717105/ephedrine-induced-mitophagy-via-oxidative-stress-in-human-hepatic-stellate-cells
#8
Ah Young Lee, Yoonjeong Jang, Seong-Ho Hong, Seung-Hee Chang, Sungjin Park, Sanghwa Kim, Kyung-Sun Kang, Ji-Eun Kim, Myung-Haing Cho
The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28715713/metastasis-systems-biology-how-are-macro-environmental-signals-transmitted-into-microenvironmental-cues-for-disseminated-tumor-cells
#9
REVIEW
Candice Alexandra Grzelak, Cyrus Michael Ghajar
Disseminated breast tumor cells reside on or near stable microvascular endothelium. Currently, the cues that disrupt DTC dormancy and facilitate outgrowth are largely unknown. This article explores the hypothesis that specific patient lifestyle exposures (e.g., alcohol abuse) may disrupt the microenvironments that maintain disseminated tumor cell (DTC) dormancy in a tissue-specific fashion. We suggest that such exposures are 'transmitted' to the dormant niche in the form of injury. Thus, we discuss the relationship between wound healing and metastasis using liver as an example to illustrate how injury steers the phenotype of liver endothelium and perivascular hepatic stellate cells to a potentially pro-metastatic one...
July 14, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28713909/effects-of-lentiviral-vector%C3%A2-mediated-shrna-silencing-of-tgf%C3%AE-1-on-the-expression-of-col1a1-in-rat-hepatic-stellate-cells
#10
Gan-Ping Bai, Guo-He Yan, Guo-Jian Wang, Ping Wan, Xiao-Fei Liu, Heng Wang, Rong-Hua Zhang
The present study aimed to construct a lentiviral RNA interference (RNAi) vector targeting the transforming growth factor β1 (TGFβ1) gene of rats, in order to examine its effect on silencing of the TGFβ1 gene and on the expression of collagen type 1 α1 (Col1a1) in HSC‑T6 rat hepatic stellate cells. Three RNAi sites of the TGFβ1 gene were selected according to its CDs sequence. Three pairs of small interfering RNA (siRNA) of these RNAi sites were synthesized and then transfected into HSC‑T6 cells, respectively, to confirm the optimal siRNA sequence via reverse transcription‑polymerase chain reaction analysis...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712861/a-novel-golgi-cox-staining-method-for-detecting-and-characterizing-roles-of-the-hepatic-stellate-cells-in-liver-injury
#11
Ma de Jesús Gómez Villalobos, Susana Vidrio, Ruth Giles López, Gabriel Flores Gómez, Victoria Chagoya de Sánchez
The aim of this study was to investigate the utility of the Golgi-Cox method to characterize the distribution and morphological changes of the hepatic stellate cells (HSCs) in CCl4 liver damaged rats. Six-week-old male Wistar rats were injected with CCl4 for ten weeks. The livers were processed with the Golgi-Cox method, reticuline, and Massońs Trichrome stains, and analyzed under light microscopy. Histological evaluation of livers was made through the METAVIR score. In normal livers, the HSCs show stellate form with abundant thin cytoplasmic processes, distributed into hepatic lobule, mainly in zone 1...
June 30, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28712391/-hepatic-stellate-cells-inhibit-the-proliferation-and-invasion-of-hepg2-hepatocellular-carcinoma-via-activating-%C3%AE-%C3%AE-t-cells
#12
Kai Fan, Rui Liao, Yuxiao Xie, Cong Peng, Chengyou Du
Objective To investigate the effects of γδ T cells co-cultured with human hepatic stellate cells (HSCs) on the proliferation and invasion of hepatocellular carcinoma (HCC) cells. Methods Peripheral γδ T cells of healthy volunteers and HCC patients were separated and collected by density gradient centrifugation and flow cytometry. Transwell(TM) chambers were used to co-culture LX-2 cells and γδ T cells. The concentration of IFN-γ in γδ T cell supernatant was detected by ELISA. The proliferation of HepG2 cells was analyzed by CCK-8 assay, and the invasion ability of HepG2 cells was evaluated by Transwell(TM) chamber assay...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28710903/stellate-cells-orchestrate-concanavalin-a-induced-acute-liver-damage
#13
Richa Rani, Ashish Tandon, Jiang Wang, Sudhir Kumar, Chandrashekhar R Gandhi
Concanavalin A (ConA) causes immune cell-mediated liver damage, but the contribution of resident nonparenchymal cells is also evident. Hepatic stellate cells (HSCs) induce hepatic inflammation and immunological reactions; we therefore investigated their role in ConA-induced liver injury. ConA was administered i.v. to control or HSC-depleted mice; hepatic histopathology and cytokines/chemokines were determined after 6 hours. In vitro, the effects of ConA-conditioned HSC medium on hepatocytes were determined...
July 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28710422/enmd-1068-inhibits-liver-fibrosis-through-attenuation-of-tgf-%C3%AE-1-smad2-3-signaling-in-mice
#14
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/28708585/the-neglected-avian-hepatotropic-virus-induces-acute-and-chronic-hepatitis-in-ducks-an-alternative-model-for-hepatology
#15
Xumin Ou, Sai Mao, Jingyu Cao, Yunchao Ma, Guangpeng Ma, Anchun Cheng, Mingshu Wang, Dekang Zhu, Shun Chen, Renyong Jia, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen
Duck Hepatitis A Virus (DHAV) belongs to the Avihepatovirus, which is also classified into Picornaviridae with Hepatovirus, Hepatitis A Virus (HAV). In humans, the pathogenesis of HAV is not well understood because of limited work with animal models. Here, we investigated the progress of duck viral hepatitis caused by DHAV and their potential for dissecting the pathogenesis of HAV. During the course of infection, the duck model had undergone hepatocellular lesions (vacuolation, acidophilic degeneration and steatosis), lymphocytes recruitment (neutrophil granulocytes, heterophilic granulocytes and T cells or plasm cells) and repair (activation of hepatic stellate cells, fibrosis and regeneration)...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708582/tumor-specific-hepatic-stellate-cells-thscs-induces-digr2-expression-in-dendritic-cells-to-inhibit-t-cells
#16
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...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704922/transcriptome-differences-in-porcine-alveolar-macrophages-from-tongcheng-and-large-white-pigs-in-response-to-highly-pathogenic-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-infection
#17
Wan Liang, Likai Ji, Yu Zhang, Yueran Zhen, Qingde Zhang, Xuewen Xu, Bang Liu
Porcine reproductive and respiratory syndrome virus (PRRSV) is a single-stranded positive-sense RNA virus that can cause devastating reproductive failure and respiratory tract lesions, which has led to serious damage to the swine industry worldwide. Our previous studies have indicated that Tongcheng (TC) pigs, a Chinese local breed, have stronger resistance or tolerance to PRRSV infection than Large White (LW) pigs. This study aims to investigate their host transcriptome differences in porcine alveolar macrophages (PAMs) at 7 days post challenge...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28702667/microengineered-cultures-containing-human-hepatic-stellate-cells-and-hepatocytes-for-drug-development
#18
Matthew D Davidson, David A Kukla, Salman R Khetani
In non-alcoholic steatohepatitis (NASH), hepatic stellate cells (HSC) differentiate into myofibroblast-like cells that cause fibrosis, which predisposes patients to cirrhosis and hepatocellular carcinoma. Thus, modeling interactions between activated HSCs and hepatocytes in vitro can aid in the development of anti-NASH/fibrosis therapeutics and lead to a better understanding of disease progression. Species-specific differences in drug metabolism and disease pathways now necessitate the supplementation of animal studies with data acquired using human liver models; however, current models do not adequately model the negative effects of primary human activated HSCs on the phenotype of otherwise well-differentiated primary human hepatocytes (PHHs) as in vivo...
July 12, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
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
#19
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/28701883/20s-protopanaxadiol-an-aglycosylated-ginsenoside-metabolite-induces-hepatic-stellate-cell-apoptosis-through-liver-kinase-b1-amp-activated-protein-kinase-activation
#20
Sang Mi Park, Eun Hye Jung, Jae Kwang Kim, Kyung Hwan Jegal, Chung A Park, Il Je Cho, Sang Chan Kim
BACKGROUND: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. METHODS: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides...
July 2017: Journal of Ginseng Research
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