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Fibrogenesis

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https://www.readbyqxmd.com/read/28099257/antifibrotic-effect-of-saturated-fatty-acids-via-endoplasmic-reticulum-stress-response-in-rat-pancreatic-stellate-cells
#1
Lingaku Lee, Tetsuhide Ito, Taichi Nakamura, Robert T Jensen, Hisato Igarashi, Ryoichi Takayanagi
OBJECTIVES: We investigated the effect of saturated fatty acids on chronic pancreatitis pathogenesis by elucidating the endoplasmic reticulum (ER) stress response in pancreatic stellate cells (PSCs), which are major effector cells in pancreatic fibrosis. METHODS: Wistar Bonn/Kobori rats were fed either control diet or high-fat diet (HFD) for 4 weeks. Meanwhile, cultured rat PSCs were stimulated with thapsigargin, an ER stress inducer, or palmitic acid (PA). Pancreatic fibrosis, expressions of fibrosis-related and ER stress-related proteins and mRNA, cell viability, and apoptosis were examined...
January 18, 2017: Pancreas
https://www.readbyqxmd.com/read/28098218/the-role-of-mir-497-5p-in-myofibroblast-differentiation-of-lr-mscs-and-pulmonary-fibrogenesis
#2
Xiang Chen, Chaowen Shi, Cong Wang, Weilin Liu, Yanhong Chu, Zou Xiang, Kebin Hu, Ping Dong, Xiaodong Han
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal fibrotic lung disease characterized by profound changes in stem cell differentiation, epithelial cell phenotypes and fibroblast proliferation. In our study, we found that miR-497-5p was significantly upregulated both during myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSCs) and in the lung tissues of a pulmonary fibrosis model. In addition, as determined by luciferase assays and Western blot analysis, reversion-inducing cysteine-rich protein with kazal motifs (Reck) was identified to be one of the target genes of miR-497-5p, and Reck could suppress the expression of matrix metalloproteinase-2 (Mmp2) and Mmp9, which could activate latent transforming growth factor-β1 (TGF-β1)...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097825/signalling-pathways-involved-in-hypoxia-induced-renal-fibrosis
#3
REVIEW
Minna Liu, Xiaoxuan Ning, Rong Li, Zhen Yang, Xiaoxia Yang, Shiren Sun, Qi Qian
Renal fibrosis is the common pathological hallmark of progressive chronic kidney disease (CKD) with diverse aetiologies. Recent researches have highlighted the critical role of hypoxia during the development of renal fibrosis as a final common pathway in end-stage kidney disease (ESKD), which joints the scientist's attention recently to exploit the molecular mechanism underlying hypoxia-induced renal fibrogenesis. The scaring formation is a multilayered cellular response and involves the regulation of multiple hypoxia-inducible signalling pathways and complex interactive networks...
January 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28077400/differential-expression-of-hedgehog-and-snail-in-cutaneous-fibrosing-disorders-implications-for-targeted-inhibition
#4
Amrita Goyal, Katy R Linskey, Jonathan Kay, Lyn M Duncan, Rosalynn M Nazarian
OBJECTIVES: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition. METHODS: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 β (GSK3-β), β-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28073161/the-pnpla3-i148m-variant-modulates-the-fibrogenic-phenotype-of-human-hepatic-stellate-cells
#5
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/28068221/devilish-effects-of-taz-in-nonalcoholic-steatohepatitis
#6
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/28066964/mechanisms-of-the-prevention-and-inhibition-of-the-progression-and-development-of-nash-by-genetic-and-pharmacological-dcr3-supplementation
#7
Pei-Chang Lee, Ling-Yu Yang, Ying-Wen Wang, Shiang-Fen Huang, Kuei-Chuan Lee, Yun-Cheng Hsieh, Ying-Ying Yang, Shie-Liang Hsieh, Ming-Chih Hou, Han-Chieh Lin, Fa-Yuah Lee, Shou-Dong Lee
AIMS: Treatment to non-alcoholic steatohepatitis (NASH) is difficult due to the absence of a proven treatment and its comprehensive mechanisms. In the NASH animal model, up-regulated hepatic inflammation and oxidative stress with the resultant M1 polarization of macrophage as well as the imbalanced adipocytokines all accelerate NASH progression. As a member of TNF receptor superfamily, decoy receptor 3 (DcR3) not only neutralizes the death ligands, but also performs immune modulations...
January 8, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28056422/propofol-inhibits-lps-induced-apoptosis-in-lung-epithelial-cell-line-beas-2b
#8
Xiang Lv, Xuhui Zhou, Jia Yan, Jue Jiang, Hong Jiang
Lipopolysaccharide (LPS) plays an important role in lung endothelial apoptosis which is crucial for lung fibrogenesis in ARDS progression. Reactive oxygen species (ROS) has been reported to be involved in LPS-induced lung epithelial cell apoptosis. Propofol is a commonly used intravenous anesthetic agent in clinic and it could attenuate LPS-induced epithelial cells oxidation and apoptosis. However, the mechanisms are still obscure. In this study, we examined whether and how propofol attenuates LPS-induced oxidation and apoptosis in BEAS-2B cells...
January 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28045017/protective-effects-of-intercalated-disk-protein-afadin-on-chronic-pressure-overload-induced-myocardial-damage
#9
Dimitar P Zankov, Akio Shimizu, Miki Tanaka-Okamoto, Jun Miyoshi, Hisakazu Ogita
Adhesive intercellular connections at cardiomyocyte intercalated disks (IDs) support contractile force and maintain structural integrity of the heart muscle. Disturbances of the proteins at IDs deteriorate cardiac function and morphology. An adaptor protein afadin, one of the components of adherens junctions, is expressed ubiquitously including IDs. At present, the precise role of afadin in cardiac physiology or disease is unknown. To explore this, we generated conditional knockout (cKO) mice with cardiomyocyte-targeted deletion of afadin...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043789/intrahepatic-upregulation-of-mrtf-a-signaling-contributes-to-increased-hepatic-vascular-resistance-in-cirrhotic-rats-with-portal-hypertension
#10
Lei Zheng, Jun Qin, Longci Sun, Liang Gui, Chihao Zhang, Yijun Huang, Wensheng Deng, An Huang, Dong Sun, Meng Luo
BACKGROUND: Portal hypertension in cirrhosis is mediated, in part, by increased intrahepatic resistance, reflecting massive structural changes associated with fibrosis and intrahepatic vasoconstriction. Activation of the Rho/MRTF/SRF signaling pathway is essential for the cellular regulatory network of fibrogenesis. The aim of this study was to investigate MRTF-A-mediated regulation of intrahepatic fibrogenesis in cirrhotic rats. METHODS: Portal hypertension was induced in rats via an injection of CCl4 oil...
December 30, 2016: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28043031/liver-5-ht7-receptors-a-novel-regulator-target-of-fibrosis-and-inflammation-induced-chronic-liver-injury-in-vivo-and-in-vitro
#11
Beyzagul Polat, Zekai Halici, Elif Cadirci, Emre Karakus, Yasin Bayir, Abdulmecit Albayrak, Deniz Unal
BACKGROUND AND AIM: Hepatocellular cancer (HCC) is the sixth most common cancer and liver fibrosis is strongly associated with HCC. Treatment options are limited, and preventive strategies should be developed. An important step in the beginning of liver fibrosis is a strong inflammatory response. 5-HT7 is the last recognized member of the serotonin receptor family and is expressed in both central nerve system and peripheral system and have a lot of functions like learning, memory, smooth muscular relaxation, in the control of circadian rhythms and thermoregulation, pain and migraine, schizophrenia, anxiety, cognitive disturbances, and even inflammation...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28041914/repression-of-tsc1-tsc2-mediated-by-mecp2-regulates-human-embryo-lung-fibroblast-cell-differentiation-and-proliferation
#12
Yuanyuan Wang, Chen Chen, Ziyu Deng, Erbao Bian, Cheng Huang, Ting Lei, Xiongwen Lv, Liping Liu, Jun Li
Pulmonary fibrosis (PF) is a severe inflammatory disease with limited effective treatments. It is known that the transdifferentiation of human embryo lung fibroblast (HELF) cells from pulmonary fibroblasts into myofibroblasts, contributes to the progression of pulmonary fibrogenesis. The tuberous sclerosis proteins TSC1 and TSC2 are two key signaling factors which can suppress cell growth and proliferation. However, the roles of TSC1 and TSC2 in lung fibroblast are unclear. Here, we developed a PF model with bleomycin (BLM) in mice and conducted several simulation experiments in HELF cells...
December 29, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28039913/the-unfolded-protein-response-mediates-fibrogenesis-and-collagen-i-secretion-through-regulating-tango1-in-mice
#13
Jessica L Maiers, Enis Kostallari, Malek Mushref, Thiago M deAssuncao, Haiyang Li, Nidhi Jalan-Sakrikar, Robert C Huebert, Sheng Cao, Harmeet Malhi, Vijay H Shah
: Fibrogenesis encompasses the deposition of matrix proteins, such as collagen I, by hepatic stellate cells (HSCs) that culminates in cirrhosis. Fibrogenic signals drive transcription of procollagen I, which enters the endoplasmic reticulum (ER), is trafficked through the secretory pathway, and released to generate extracellular matrix. Alternatively, disruption of procollagen I ER export could activate the unfolded protein response (UPR) and drive HSC apoptosis. Using a small interfering RNA screen, we identified Transport and Golgi organization 1 (TANGO1) as a potential participant in collagen I secretion...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28030556/hepatocyte-hypoxia-inducible-factor-1-mediates-the-development-of-liver-fibrosis-in-a-mouse-model-of-nonalcoholic-fatty-liver-disease
#14
Omar A Mesarwi, Mi-Kyung Shin, Shannon Bevans-Fonti, Christina Schlesinger, Janet Shaw, Vsevolod Y Polotsky
BACKGROUND: Obstructive sleep apnea (OSA) is associated with the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia. Emerging data has implicated hepatocyte cell signaling as an important factor in hepatic fibrogenesis. We hypothesized that hepatocyte specific knockout of the oxygen sensing α subunit of hypoxia inducible factor-1 (HIF-1), a master regulator of the global response to hypoxia, may be protective against the development of liver fibrosis...
2016: PloS One
https://www.readbyqxmd.com/read/28029729/combination-treatment-of-dipeptidyl-peptidase-iv-inhibitor-sitagliptin-and-angiotensin-ii-type-1-receptor-blocker-losartan-suppresses-progression-in-a-nondiabetic-rat-model-of-steatohepatitis
#15
Yasushi Okura, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Ryuichi Noguchi, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Shinya Sato, Yasuhiko Sawada, Naotaka Shimozato, Masanori Furukawa, Keisuke Nakanishi, Saikawa Soichiro, Takuya Kubo, Kiyoshi Asada, Hitoshi Yoshiji
AIM: Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we demonstrated that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (ARB: losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis. We aimed to elucidate the effects and possible mechanisms of a sitagliptin + losartan combination on the progression of nondiabetic nonalcoholic steatohepatitis (NASH) in a rat model...
December 28, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28027574/new-classification-of-liver-biopsy-assessment-for-fibrosis-in-chronic-hepatitis-b-patients-before-and-after-treatment
#16
Yameng Sun, Jialing Zhou, Lin Wang, Xiaoning Wu, Yongpeng Chen, Hongxin Piao, Lungen Lu, Wei Jiang, Youqing Xu, Bo Feng, Yuemin Nan, Wen Xie, Guofeng Chen, Huanwei Zheng, Hai Li, Huiguo Ding, Hui Liu, Fudong Lv, Chen Shao, Tailing Wang, Xiaojuan Ou, Bingqiong Wang, Shuyan Chen, Aileen Wee, Neil D Theise, Hong You, Jidong Jia
: Liver fibrosis is the net result of dynamic changes between fibrogenesis and fibrolysis. Evidence has shown that antiviral therapy can reverse liver fibrosis or even early cirrhosis. However, the current evaluation systems mainly focus on the severity, but not the dynamic changes of fibrosis. Here, we propose a new classification to evaluate the dynamic changes in the quality of fibrosis, namely: predominantly progressive (thick/broad/loose/pale septa with inflammation), predominately regressive (delicate/thin/dense/splitting septa), and indeterminate which displayed an overall balance between progressive and regressive scarring...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28024287/tetramethylpyrazine-attenuates-carbon-tetrachloride-caused-liver-injury-and-fibrogenesis-and-reduces-hepatic-angiogenesis-in-rats
#17
Shifeng Zhao, Zili Zhang, Linnan Qian, Qiuyi Lin, Chenxi Zhang, Jiangjuan Shao, Feng Zhang, Shizhong Zheng
Liver fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with abnormalities of angiogenesis in the liver. Capillarization of liver sinusoidal endothelial cell (LSEC) is the pivotal event during liver angiogenesis. In the current study, we sought to investigate the effect of tetramethylpyrazine (TMP) on carbon tetrachloride (CCl4)-induced liver injury and fibrosis in rats, and to further examine the molecular mechanisms of TMP-induced anti-angiogenic effect. We found that TMP significantly ameliorated histopathological feature of liver fibrosis characterized by decreased collagen deposition, hepatocyte apoptosis, and expression of biochemical indicators, such as aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)...
December 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28017695/mir-29c-is-implicated-in-the-cardioprotective-activity-of-panax-notoginseng-saponins-against-isoproterenol-induced-myocardial-fibrogenesis
#18
Li Liu, Bingbing Ning, Jingang Cui, Teng Zhang, Yu Chen
ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (Burkill) F.H. Chen (Araliaceae) has a long history of clinical application in China for the treatment of cardiovascular diseases. Panax notoginseng saponins (PNS) have been proven to be the major cardioprotective substances of Panax notoginseng (Burkill) F.H. Chen (Araliaceae). AIM OF THE STUDY: The current study further investigated the molecular mechanisms associated with the cardioprotective effect of PNS. MATERIALS AND METHODS: C57BL/6J mice were subject to isoproterenol (ISO)-induced myocardial injury in the absence or presence of PNS treatment...
December 22, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28011329/functional-role-of-ccl5-rantes-for-hcc-progression-during-chronic-liver-disease
#19
Antje Mohs, Nadine Kuttkat, Johanna Reißing, Henning Wolfgang Zimmermann, Roland Sonntag, Amanda Proudfoot, Sameh A Youssef, Alain de Bruin, Francisco Javier Cubero, Christian Trautwein
BACKGROUND & AIMS: During liver inflammation, triggering fibrogenesis and carcinogenesis immune cells play a pivotal role. In the present study we investigated the role of CCL5 in human and in murine models of chronic liver inflammation leading to HCC development. METHODS: CCL5 expression and its receptors were studied in well-defined patients with chronic liver disease (CLD) and in two murine inflammation based HCC models. The role of CCL5 in inflammation, fibrosis, tumor initiation and progression was analyzed in different cell populations of NEMO(Δhepa)/CCL5(-/-) animals and after bone marrow transplantation (BMT)...
December 20, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28000758/chronic-hepatitis-c-infection-induced-liver-fibrogenesis-is-associated-with-m2-macrophage-activation
#20
Moses T Bility, Kouki Nio, Feng Li, David R McGivern, Stanley M Lemon, Eoin R Feeney, Raymond T Chung, Lishan Su
The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV-induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV-induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation...
December 21, 2016: Scientific Reports
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