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Fibrogenesis

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https://www.readbyqxmd.com/read/28647181/rosmarinic-acid-attenuates-hepatic-fibrogenesis-via-suppression-of-hepatic-stellate-cell-activation-proliferation-and-induction-of-apoptosis
#1
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/28640451/cardiac-fibrosis-and-arrhythmogenesis
#2
My-Nhan Nguyen, Helen Kiriazis, Xiao-Ming Gao, Xiao-Jun Du
Myocardial injury, mechanical stress, neurohormonal activation, inflammation, and/or aging all lead to cardiac remodeling, which is responsible for cardiac dysfunction and arrhythmogenesis. Of the key histological components of cardiac remodeling, fibrosis either in the form of interstitial, patchy, or dense scars, constitutes a key histological substrate of arrhythmias. Here we discuss current research findings focusing on the role of fibrosis, in arrhythmogenesis. Numerous studies have convincingly shown that patchy or interstitial fibrosis interferes with myocardial electrophysiology by slowing down action potential propagation, initiating reentry, promoting after-depolarizations, and increasing ectopic automaticity...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28639412/the-role-of-microrna-5196-in-the-pathogenesis-of-systemic-sclerosis
#3
Marzena Ciechomska, Patryk Zarecki, Michal Merdas, Jerzy Swierkot, Ewa Morgiel, Piotr Wiland, Wlodzimierz Maslinski, Katarzyna Bogunia-Kubik
BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by tissue fibrosis and immune abnormalities. Recent evidence suggests that activated circulating monocytes from SSc patients play an important role in early stages of SSc pathogenesis due to enhanced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1), IL-8 and reactive oxygen species (ROS) induction. However, the exact factors that contribute to chronic inflammation and subsequently fibrosis progression are still unknown...
June 21, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28635165/therapeutic-targeting-of-the-mitochondrial-reactive-oxygen-species-engine-prevents-portal-hypertension-and-hepatic-fibrogenesis
#4
EDITORIAL
Ralf Weiskirchen
No abstract text is available yet for this article.
July 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28629226/no-significant-impact-of-foxf1-sirna-treatment-in-acute-and-chronic-ccl4-liver-injury
#5
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/28624207/identification-of-novel-fibrosis-modifiers-by-in%C3%A2-vivo-sirna-silencing
#6
Elisabeth H Vollmann, Lizhi Cao, Aldo Amatucci, Taylor Reynolds, Stefan Hamann, Isin Dalkilic-Liddle, Thomas O Cameron, Markus Hossbach, Kevin J Kauffman, Faryal F Mir, Daniel G Anderson, Tatiana Novobrantseva, Victor Koteliansky, Tatiana Kisseleva, David Brenner, Jeremy Duffield, Linda C Burkly
Fibrotic diseases contribute to 45% of deaths in the industrialized world, and therefore a better understanding of the pathophysiological mechanisms underlying tissue fibrosis is sorely needed. We aimed to identify novel modifiers of tissue fibrosis expressed by myofibroblasts and their progenitors in their disease microenvironment through RNA silencing in vivo. We leveraged novel biology, targeting genes upregulated during liver and kidney fibrosis in this cell lineage, and employed small interfering RNA (siRNA)-formulated lipid nanoparticles technology to silence these genes in carbon-tetrachloride-induced liver fibrosis in mice...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28624101/reversal-of-liver-fibrosis-from-fiction-to-reality
#7
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/28621467/critical-role-of-crebh-mediated-induction-of-tgf-%C3%AE-2-by-hcv-infection-in-fibrogenic-responses-in-hepatic-stellate-cells
#8
Takeshi Chida, Masahiko Ito, Kenji Nakashima, Yumi Kanegae, Takuya Aoshima, Shuji Takabayashi, Kazuhito Kawata, Yoshimi Nakagawa, Masahiro Yamamoto, Hitoshi Shimano, Tomokazu Matsuura, Yoshimasa Kobayashi, Takafumi Suda, Tetsuro Suzuki
Mechanisms of hepatic fibrogenesis induced by Hepatitis C virus (HCV), one of the leading causes of liver fibrosis, are not fully understood. We studied transcriptional up-regulation of transforming growth factor β (TGF-β), especially TGF-β2, which is mediated via the activation of liver-enriched transcription factor CREBH triggered by HCV infection and its functional significance for induction of profibrogenic phenotypes via interaction of HCV-infected cells with hepatic stellate cells (HSC). Compared to TGF-β1, expression of TGF-β2 mRNA was induced faster and to a higher level upon HCV infection...
June 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28618656/role-of-growth-factor-receptor-bound-2-in-ccl4-induced-hepatic-fibrosis
#9
Shanfei Ge, Ying Xiong, Xiaoping Wu, Jianping Xie, Fei Liu, Jinni He, Tianxing Xiang, Na Cheng, Lingling Lai, Yuanbin Zhong
BACKGROUND: Growth Factor Receptor-bound 2 (GRB2) plays a crucial role in regulation of cellular function including proliferation and differentiation, and we previously identified GRB2 as promoting HSCs (HSCs) proliferation. However, the underlying mechanisms that are involving in the regulation of GRB2 in hepatic fibrogenesis remain unknown. METHODS: In the present study, we tested the function of GRB2 in hepatic fibrosis. Hepatic fibrosis was induced by subcutaneous CCl4 administration at a dose of 3mL/kg in rats...
June 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28617446/cathepsin-l-and-b-as-potential-markers-for-liver-fibrosis-insights-from-patients-and-experimental-models
#10
Mansi Manchanda, Prasenjit Das, Gaurav P S Gahlot, Ratnakar Singh, Elke Roeb, Martin Roderfeld, Siddhartha Datta Gupta, Anoop Saraya, R M Pandey, Shyam S Chauhan
OBJECTIVES: Cathepsin L (CTSL) and B (CTSB) have a crucial role in extracellular matrix (ECM) degradation and tissue remodeling, which is a prominent feature of fibrogenesis. The aim of this study was to determine the role and clinical significance of these cathepsins in liver fibrosis. METHODS: Hepatic histological CTSL and CTSB expression were assessed in experimental models of liver fibrosis, patients with liver cirrhosis, chronic viral hepatitis, and controls by real-time PCR and immunohistochemistry...
June 15, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28615649/andrographolide-ameliorates-inflammation-and-fibrogenesis-and-attenuates-inflammasome-activation-in-experimental-non-alcoholic-steatohepatitis
#11
Daniel Cabrera, Alexander Wree, Davide Povero, Nancy Solís, Alejandra Hernandez, Margarita Pizarro, Han Moshage, Javiera Torres, Ariel E Feldstein, Claudio Cabello-Verrugio, Enrique Brandan, Francisco Barrera, Juan Pablo Arab, Marco Arrese
Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-amino-acid-defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-times/week)...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612750/genetic-and-epigenetic-profile-of-patients-with-alcoholic-liver-disease
#12
Luigi Boccuto, Ludovico Abenavoli
Alcoholic liver disease (ALD) is a definition encompassing a spectrum of disorders ranging from simple steatosis to cirrhosis and hepatocellular carcinoma. Excessive alcohol consumption triggers a series of metabolic reactions that affect the liver by inducing lipogenesis, increasing oxidative stress, and causing abnormal inflammatory responses. The metabolic pathways regulating lipids, reactive oxygen species (ROS), and immune system are closely related and in some cases cross-regulate each other. Therefore, it must be taken into account that major genetic and epigenetic abnormalities affecting enzymes involved in one of such pathways can play a pivotal role in ALD pathogenesis...
August 1, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28611663/epigenetic-modifications-to-h3k9-in-renal-tubulointerstitial-cells-after-unilateral-ureteric-obstruction-and-tgf-%C3%AE-1-stimulation
#13
Timothy D Hewitson, Stephen G Holt, Sven-Jean Tan, Belinda Wigg, Chrishan S Samuel, Edward R Smith
Introduction: Epigenetic regulation of fibrogenesis through post-translational histone modifications (marks) may be a key determinant of progression in renal disease. In this study, we examined the distribution and acquisition of histone 3 Lysine 9 (H3K9) marks after injury and stimulation with the pro-fibrotic cytokine TGF-β1. Our focus was on their presence in activated fibroblasts (myofibroblasts) and epithelial cells (epithelial-mesenchymal transition). Methods and Results: Immunofluorescent microscopy was used to examine global H3K9 acetylation (H3K9Ac) and tri-methylation (H3K9Me3) after unilateral ureteric obstruction (UUO) in mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28611447/serpinb3-promotes-pro-fibrogenic-responses-in-activated-hepatic-stellate-cells
#14
Erica Novo, Gianmarco Villano, Cristian Turato, Stefania Cannito, Claudia Paternostro, Chiara Busletta, Alessandra Biasiolo, Santina Quarta, Elisabetta Morello, Claudia Bocca, Antonella Miglietta, Ezio David, Salvatore Sutti, Mario Plebani, Emanuele Albano, Maurizio Parola, Patrizia Pontisso
SerpinB3 is a hypoxia- and hypoxia-inducible factor-2α-dependent cystein protease inhibitor that is up-regulated in hepatocellular carcinoma and in parenchymal cells during chronic liver diseases (CLD). SerpinB3 up-regulation in CLD patients has been reported to correlate with the extent of liver fibrosis and the production of transforming growth factor-β1, but the actual role of SerpinB3 in hepatic fibrogenesis is still poorly characterized. In the present study we analyzed the pro-fibrogenic action of SerpinB3 in cell cultures and in two different murine models of liver fibrosis...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611350/fgf23-is-synthesised-locally-by-renal-tubules-and-activates-injury-primed-fibroblasts
#15
Edward R Smith, Sven-Jean Tan, Stephen G Holt, Tim D Hewitson
In kidney disease, higher circulating levels of the mineral-regulating hormone fibroblast growth factor (FGF)-23 are predictive of disease progression but direct pathogenic effects on the kidney are unknown. We sought evidence of local renal synthesis in response to unilateral ureteric obstruction in the mouse, and pro-fibrotic actions of FGF23 on the fibroblast in vitro. Acute tubulointerstitial injury due to unilateral ureteric obstruction stimulated renal FGF23 synthesis by tubules, and downregulated inactivating proprotein convertases, without effects on systemic mineral metabolism...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28598023/nintedanib-reduces-ventilation-augmented-bleomycin-induced-epithelial-mesenchymal-transition-and-lung-fibrosis-through-suppression-of-the-src-pathway
#16
Li-Fu Li, Kuo-Chin Kao, Yung-Yang Liu, Chang-Wei Lin, Ning-Hung Chen, Chung-Shu Lee, Chih-Wei Wang, Cheng-Ta Yang
Mechanical ventilation (MV) used in patients with acute respiratory distress syndrome (ARDS) can increase lung inflammation and pulmonary fibrogenesis. Src is crucial in mediating the transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) during the fibroproliferative phase of ARDS. Nintedanib, a multitargeted tyrosine kinase inhibitor that directly blocks Src, has been approved for the treatment of idiopathic pulmonary fibrosis. The mechanisms regulating interactions among MV, EMT and Src remain unclear...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28596109/cytotherapy-with-m1-polarized-macrophages-ameliorates-liver-fibrosis-by-modulating-immune-microenvironment-in-mice
#17
Peng-Fei Ma, Chun-Chen Gao, Jing Yi, Jun-Long Zhao, Shi-Qian Liang, Yang Zhao, Yu-Chen Ye, Jian Bai, Qi-Jun Zheng, Ke-Feng Dou, Hua Han, Hong-Yan Qin
BACKGROUND & AIMS: Macrophages play vital roles in chronic liver injury, and have been tested as a tool for cytotherapy of liver fibrosis. However, macrophages possess ontogenic and functional heterogeneities. Some subsets are pro-fibrotic, whereas others are anti-fibrotic. This study aimed at clarifying which macrophage subset is efficient in cytotherapy of liver fibrosis and the underlying mechanisms. METHODS: Liver fibrosis was induced in mice by carbon tetrachloride (CCl4) injection or bile duct ligation (BDL)...
June 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28593184/epigenetics-and-liver-fibrosis
#18
REVIEW
Eva Moran-Salvador, Jelena Mann
Liver fibrosis arises because prolonged injury combined with excessive scar deposition within hepatic parenchyma arising from overactive wound healing response mediated by activated myofibroblasts. Fibrosis is the common end point for any type of chronic liver injury including alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, and cholestatic liver diseases. Although genetic influences are important, it is epigenetic mechanisms that have been shown to orchestrate many aspects of fibrogenesis in the liver...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28592801/immune-cell-derived-cytokines-contribute-to-obesity-related-inflammation-fibrogenesis-and-metabolic-deregulation-in-human-adipose-tissue
#19
Charles Caër, Christine Rouault, Tiphaine Le Roy, Christine Poitou, Judith Aron-Wisnewsky, Adriana Torcivia, Jean-Christophe Bichet, Karine Clément, Michèle Guerre-Millo, Sébastien André
Adipose tissue contains a variety of immune cells, which vary in abundance and phenotype with obesity. The contribution of immune cell-derived factors to inflammatory, fibrotic and metabolic alterations in adipose tissue is not well established in human obesity. Human primary adipose tissue cells, including pre-adipocytes, endothelial cells and mature adipocytes, were used to investigate deregulation of cell- and pathway-specific gene profiles. Among factors known to alter adipose tissue biology, we focus on inflammatory (IL-1β and IL-17) and pro-fibrotic (TGF-β1) factors...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592228/anti-fibrogenic-effect-of-ppar-%C3%AE-agonists-in-human-intestinal-myofibroblasts
#20
Jun Bon Koo, Myeong-Ok Nam, Younshin Jung, Jongman Yoo, Duk Hwan Kim, Gwangil Kim, Sung Jae Shin, Kee Myung Lee, Ki Baik Hahm, Jong Woo Kim, Sung Pyo Hong, Kwang Jae Lee, Jun Hwan Yoo
BACKGROUND: Intestinal fibrosis is a serious complication of inflammatory bowel disease, including Crohn's disease and ulcerative colitis. There is no specific treatment for intestinal fibrosis. Studies have indicated that peroxisome proliferator-activated receptor- γ (PPAR-γ) agonists have anti-fibrogenic properties in organs besides the gut; however, their effects on human intestinal fibrosis are poorly understood. This study investigated the anti-fibrogenic properties and mechanisms of PPAR-γ agonists on human primary intestinal myofibroblasts (HIFs)...
June 7, 2017: BMC Gastroenterology
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