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Hepatic stellate cell

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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
#1
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...
June 21, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28647181/rosmarinic-acid-attenuates-hepatic-fibrogenesis-via-suppression-of-hepatic-stellate-cell-activation-proliferation-and-induction-of-apoptosis
#2
Naglaa M El-Lakkany, Walaa H El-Maadawy, Sayed H Seif El-Din, Olfat A Hammam, Salwa H Mohamed, Shahira M Ezzat, Marwa M Safar, Samira Saleh
OBJECTIVE: To investigate the antifibrotic role of rosmarinic acid (RA), a natural polyphenolic compound, on HSCs activation/proliferation and apoptosis in vitro and in vivo. METHODS: The impact of RA on stellate cell line (HSC-T6) proliferation, activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo, rats were divided into: (i) normal; (ii) thioacetamide (TAA)-intoxicated rats for 12 weeks; (iii) TAA + silymarin or (iv) TAA + RA...
May 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28642549/focal-adhesion-kinase-regulates-hepatic-stellate-cell-activation-and-liver-fibrosis
#3
Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28639108/fructose-1-6-bisphosphate-reverts-iron-induced-phenotype-of-hepatic-stellate-cells-by-chelating-ferrous-ions
#4
Henrique Bregolin Dias, Gabriele Catyana Krause, Eamin Daidrê Squizani, Kelly Goulart Lima, Aline Daniele Schuster, Leonardo Pedrazza, Bruno de Souza Basso, Bianca Andrade Martha, Fernanda Cristina de Mesquita, Fernanda Bordignon Nunes, Márcio Vinicius Fagundes Donadio, Jarbas Rodrigues de Oliveira
Hepatic fibrosis is an extracellular matrix deposition by hepatic stellate cells (HSC). Fibrosis can be caused by iron, which will lead to hydroxyl radical production and cell damage. Fructose-1,6-bisphosphate (FBP) has been shown to deliver therapeutic effects in many pathological situations. In this work, we aimed to test the effects of FBP in HSC cell line, GRX, exposed to an excess of iron (Fe). The Fe-treatment increased cell proliferation and FBP reversed this effect, which was not due to increased necrosis, apoptosis or changes in cell cycle...
June 21, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28638086/wnt2b-attenuates-hscs-activation-and-liver-fibrosis-through-negative-regulating-tlr4-signaling
#5
Yi Yuan, Qiuju Han, Siyu Li, Zhigang Tian, Jian Zhang
The Wingless-type MMTV integration site family member 2b (Wnt2b) has been found to be a principal mediator of liver development and regeneration. However, the significance of Wnt2b in the pathogenesis of fibrosis-related liver diseases remains undefined. Here, we report that Wnt2b was highly expressed in the fibrotic liver tissues, exhibiting protective effects against activation of hepatic stellate cells (HSCs) and fibrosis progression. We identified a negative regulation of Wnt2b on the toll-like receptor 4 (TLR4) activation-mediated pro-fibrogenic effects...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636545/reversal-effect-of-jagged1-signaling-inhibition-on-ccl4-induced-hepatic-fibrosis-in-rats
#6
Guiju Tang, Zhihong Weng, Jun Song, Yixiong Chen
The role of the Notch ligand Jagged1 in hepatic fibrosis remains to be elucidated. In the current study, we investigated the role of Jagged1 in the activation of hepatic stellate cells (HSCs) and development of hepatic fibrosis in rats. In vitro, Jagged1 in HSCs was downregulated and upregulated by Jagged1 siRNA and pcDNA3.1 Jagged1, respectively. The levels of epithelial-mesenchymal transition (EMT) markers and HSC activation markers were assessed using western blot analysis. The proliferation and migration capacity of HSCs were assessed using 5-ethynyl-2'-deoxyuridine (EdU) incorporation and Transwell migration assays...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634394/the-roles-of-toll-like-receptor-4-in-the-pathogenesis-of-pathogen-associated-biliary-fibrosis-caused-by-clonorchis-sinensis
#7
Chao Yan, Bo Li, Fang Fan, Ying Du, Rui Ma, Xiao-Dan Cheng, Xiang-Yang Li, Bo Zhang, Qian Yu, Yu-Gang Wang, Ren-Xian Tang, Kui-Yang Zheng
Pathogen-associated biliary fibrosis (PABF) is a type of liver fibrosis characterized by injuries of cholangiocytes and extra cellular matrix (ECM) deposition around bile ducts caused by various bacteria, fungi, virus and parasites. Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear. In the present study, a PABF mouse model was established by a trematode infection-Clonorchis sinensis which dwells in the bile ducts and causes severe biliary fibrosis of mice...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634212/prolonged-darkness-reduces-liver-fibrosis-in-a-mouse-model-of-primary-sclerosing-cholangitis-by-mir-200b-down-regulation
#8
Nan Wu, Fanyin Meng, Tianhao Zhou, Yuyan Han, Lindsey Kennedy, Julie Venter, Heather Francis, Sharon DeMorrow, Paolo Onori, Pietro Invernizzi, Francesca Bernuzzi, Romina Mancinelli, Eugenio Gaudio, Antonio Franchitto, Shannon Glaser, Gianfranco Alpini
Melatonin therapy or prolonged exposure to complete darkness reduces biliary hyperplasia and liver fibrosis in bile-duct-ligated (BDL) rats; however, no information exists in primary sclerosing cholangitis (PSC). Thus, we aimed to determine the therapeutic effects of prolonged dark therapy or melatonin administration on hepatic fibrosis in the Mdr2(-/-) mouse model of PSC. Melatonin levels, biliary mass, liver fibrosis, angiogenesis and miR-200b expression were evaluated in wild-type and Mdr2(-/-) mice exposed to darkness or melatonin treatment or in male PSC patient samples and healthy controls...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28632197/toxic-age-tage-theory-for-the-pathophysiology-of-the-onset-progression-of-nafld-and-ald
#9
REVIEW
Masayoshi Takeuchi, Jun-Ichi Takino, Akiko Sakasai-Sakai, Takanobu Takata, Mikihiro Tsutsumi
Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are among the most common causes of chronic liver diseases in the westernized world. NAFLD and ALD are frequently accompanied by extrahepatic complications, including hepatocellular carcinoma and cardiovascular diseases, which have a negative impact on patient survival. The chronic ingestion of an excessive daily diet containing sugar/high-fructose corn syrup increases the level of the fructose/glucose metabolite, glyceraldehyde (GA), while the chronic consumption of an excessive number of alcoholic beverages increases the level of the alcohol metabolite, acetaldehyde (AA) in the liver...
June 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28630423/thymosin-beta-4-regulates-activation-of-hepatic-stellate-cells-via-hedgehog-signaling
#10
Jieun Kim, Jeongeun Hyun, Sihyung Wang, Chanbin Lee, Jae-Wook Lee, Eun-Yi Moon, Heejae Cha, Anna Mae Diehl, Youngmi Jung
The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA-treated LX-2. TB4 suppression down-regulated both integrin linked kinase (ILK), an activator of smoothened, and phosphorylated glycogen synthase kinase 3 beta (pGSK-3B), an inactive form of GSK-3B degrading glioblastoma 2 (GLI2), followed by the decreased expression of both smoothened and GLI2...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629226/no-significant-impact-of-foxf1-sirna-treatment-in-acute-and-chronic-ccl4-liver-injury
#11
Kerstin Abshagen, Tobias Rotberg, Berit Genz, Brigitte Vollmar
Chronic liver injury of any etiology is the main trigger of fibrogenic responses and thought to be mediated by hepatic stellate cells. Herein, activating transcription factors like forkhead box f1 are described to stimulate pro-fibrogenic genes in hepatic stellate cells. By using a liver-specific siRNA delivery system (DBTC), we evaluated whether forkhead box f1 siRNA treatment exhibit beneficial effects in murine models of acute and chronic CCl4-induced liver injury. Systemic administration of DBTC-forkhead box f1 siRNA in mice was only sufficient to silence forkhead box f1 in acute CCl4 model, but was not able to attenuate liver injury as measured by liver enzymes and necrotic liver cell area...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28628927/curcumin-promotes-apoptosis-of-activated-hepatic-stellate-cells-by-inhibiting-protein-expression-of-the-myd88-pathway
#12
Ya-Jun He, Kenny Kuchta, Yan-Mei Deng, Silke Cameron, Yu Lin, Xu-You Liu, Guo-Ron Ye, Xia Lv, Yuta Kobayashi, Jian-Chang Shu
Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC in vitro, its influence on the MyD88 pathway in HSC has remained unclear. Here, we investigated whether curcumin accelerates apoptosis of HSC through the MyD88 pathway...
June 19, 2017: Planta Medica
https://www.readbyqxmd.com/read/28627746/hepatic-perivascular-mesenchymal-stem-cells-with-myogenic-properties
#13
Sudheer Shenoy P, Bipasha Bose
Pericytes are multipotent mesenchymal stem cells (MSCs) located on the walls of blood vessels in various organs and are characterized as CD146(+) cells.. In this study, we have first immunohistochemically detected such pericytes in the perivascular regions of liver from two mouse genotypes namely wild-type (WT) and myostatin null (Mstn(-/-) ). We further isolated such pericytes using sorting as CD146(+) CD34(-) CD56(-) CD45(-) cells. The main finding of this study involve the contrasting -fibrogenic versus myogenic behavior of liver pericytes from WTMstn(-/-) ) mouse respectively...
June 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28627645/therapeutic-strategies-for-alcoholic-liver-disease-focusing-on-inflammation-and-fibrosis-review
#14
Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Masakazu Uejima, Mitsuteru Kitade, Kousuke Takeda, Yasushi Okura, Kousuke Kaji, Hiroaki Takaya, Norihisa Nishimura, Shinya Sato, Yasuhiko Sawada, Kenichiro Seki, Takuya Kubo, Akira Mitoro, Junichi Yamao, Hitoshi Yoshiji
Excessive alcohol consumption is the most common cause of liver disease in the world. Chronic alcohol abuse leads to liver damage, liver inflammation, fibrosis and hepatocellular carcinoma. Inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, induce liver injury, which leads to the develo-pment of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as interleukin (IL)-6 and IL-10, are also associated with ALD. IL-6 improves ALD via the activation of STAT3 and the subsequent induction of a variety of hepatoprotective genes in hepatocytes...
June 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28627620/protective-effect-of-human-serum-amyloid-p-on-ccl4-induced-acute-liver-injury-in-mice
#15
Min Cong, Weihua Zhao, Tianhui Liu, Ping Wang, Xu Fan, Qingling Zhai, Xiaoli Bao, Dong Zhang, Hong You, Tatiana Kisseleva, David A Brenner, Jidong Jia, Hui Zhuang
Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression...
June 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28624101/reversal-of-liver-fibrosis-from-fiction-to-reality
#16
REVIEW
Miguel Eugenio Zoubek, Christian Trautwein, Pavel Strnad
In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM...
April 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28623940/clonorchis-sinensis-lysophospholipase-a-upregulates-il-25-expression-in-macrophages-as-a-potential-pathway-to-liver-fibrosis
#17
Lina Zhou, Mengchen Shi, Lu Zhao, Zhipeng Lin, Zeli Tang, Hengchang Sun, Tingjin Chen, Zhiyue Lv, Jin Xu, Yan Huang, Xinbing Yu
BACKGROUND: Liver fibrosis is an excessive wound-healing reaction that requires the participation of inflammatory cells and hepatic stellate cells (HSCs). The pathogenesis of liver fibrosis caused by viruses and alcohol has been well characterized, but the molecular mechanisms underlying liver fibrosis induced by the liver fluke Clonorchis sinensis are poorly understood. Lysophospholipase A (LysoPLA), which deacylates lysophospholipids, plays a critical role in mediating the virulence and pathogenesis of parasites and fungi; however, the roles of C...
June 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28623783/scoparone-attenuates-hepatic-stellate-cell-activation-through-inhibiting-tgf-%C3%AE-smad-signaling-pathway
#18
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...
June 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28623272/exosomes-derived-from-palmitic-acid-treated-hepatocytes-induce-fibrotic-activation-of-hepatic-stellate-cells
#19
Young-Sun Lee, So Yeon Kim, Eunjung Ko, Jun-Hee Lee, Hyon-Seung Yi, Yang Jae Yoo, Jihye Je, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Won-Il Jeong, Jong Eun Yeon, Soon Ho Um, Kwan Soo Byun
Non-alcoholic fatty liver disease (NAFLD) is a dominant cause of chronic liver disease, but the exact mechanism of progression from simple steatosis to nonalcoholic steatohepatitis (NASH) remains unknown. Here, we investigated the role of exosomes in NAFLD progression. Exosomes were isolated from a human hepatoma cell line treated with palmitic acid (PA) and their miRNA profiles examined by microarray. The human hepatic stellate cell (HSC) line (LX-2) was then treated with exosome isolated from hepatocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623179/modulation-of-tgf-%C3%AE-smad-and-erk-signaling-pathways-mediates-the-anti-fibrotic-effect-of-mirtazapine-in-mice
#20
Dalia M El-Tanbouly, Walaa Wadie, Rabab H Sayed
Serotonin (5-HT) has been implicated as a key driver of liver fibrosis, acting via 5-HT2 receptor activation in the hepatic stellate cells. The current study was conducted to investigate the effects of mirtazapine, a 5-HT2A antagonist, in a mouse model of liver fibrosis. Mice received thioacetamide (TAA, 150mg/kg/biweekly, ip) for nine successive weeks for induction of liver fibrosis. Administration of mirtazapine significantly improved the plasma aminotransferases, reduced hepatic 5-HT concentration and ameliorated TAA-induced liver fibrosis, as demonstrated by reduced portal blood pressure, liver procollagen I content and α alpha smooth muscle actin expression...
June 13, 2017: Toxicology and Applied Pharmacology
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