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miRNA,Hepatic fibrosis

Kevin Appourchaux, Safi Dokmak, Matthieu Resche-Rigon, Xavier Treton, Martine Lapalus, Charles-Henry Gattolliat, Emmanuelle Porchet, Michelle Martinot-Peignoux, Nathalie Boyer, Michel Vidaud, Pierre Bedossa, Patrick Marcellin, Ivan Bièche, Emilie Estrabaud, Tarik Asselah
Staging fibrosis is crucial for the prognosis and to determine the rapid need of treatment in patients with chronic hepatitis B (CHB) and C (CHC). The expression of 13 fibrosis-related microRNAs (miRNAs) (miR-20a, miR-21, miR-27a, miR-27b, miR-29a, miR-29c, miR-92a, miR-122, miR-146a, miR-155, miR-221, miR-222, and miR-224) was analyzed in 194 serums and 177 liver biopsies of patients with either CHB or CHC to develop models to diagnose advanced fibrosis and cirrhosis (Metavir F3-F4). In CHB patients, the model (serum miR-122, serum miR-222, platelet count and alkaline phosphatase) was more accurate than APRI and FIB-4 to discriminate in between mild and moderate fibrosis (F1-F2) and F3-F4 (AUC of CHB model: 0...
October 12, 2016: Scientific Reports
Tomohiro Katsumi, Masashi Ninomiya, Taketo Nishina, Kei Mizuno, Kyoko Tomita, Hiroaki Haga, Kazuo Okumoto, Takafumi Saito, Tooru Shimosegawa, Yoshiyuki Ueno
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized pathologically by destruction of intrahepatic bile ducts. PBC is largely classified into three subtypes based on clinical course: (i) gradually progressive, (ii) portal hypertension, and (iii) hepatic failure. Previous studies have indicated that serum levels of the pro-inflammatory cytokine TNF-α, is elevated in PBC patients with fibrosis. Although the severity of cholangitis might also be related to the PBC subtype, its etiology has been unclear...
September 26, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Na Fu, Xuemin Niu, Yang Wang, Huijuan Du, Baoyu Wang, Jinghua Du, Ya Li, Rongqi Wang, Yuguo Zhang, Suxian Zhao, Dianxing Sun, Liang Qiao, Yuemin Nan
Long non-coding RNA (LncRNA)-activated by transforming growth factor-beta (LncRNA-ATB) is a key regulator of transforming growth factor-beta (TGF-β) signaling pathway, and is positively correlated with the development of liver cirrhosis and vascular invasion of hepatocellular carcinoma (HCC). However, the role of LncRNA-ATB in hepatitis C virus (HCV)-related liver fibrosis remains largely unknown. In the present study, we confirmed a high expression level of LncRNA-ATB in the liver tissues and plasma samples of patients with HCV-related hepatic fibrosis, and the plasma level of LncRNA-ATB was significantly correlated with liver fibrosis stages...
August 2016: Discovery Medicine
Jeongeun Hyun, Youngmi Jung
Liver fibrosis is a repair process in response to damage in the liver; however, severe and chronic injury promotes the accumulation of fibrous matrix, destroying the normal functions and architecture of liver. Hepatic stellate cells (HSCs) are quiescent in normal livers, but in damaged livers, they transdifferentiate into myofibroblastic HSCs, which produce extracellular matrix proteins. Hedgehog (Hh) signaling orchestrates tissue reconstruction in damaged livers and contributes to liver fibrogenesis by regulating HSC activation...
August 7, 2016: World Journal of Gastroenterology: WJG
Shuangpeng Cai, Xiaoyu Cheng, Xueyin Pan, Jun Li
Exosomes can meditate intercellular communication by conveying various bioactive molecules. Plentiful evidences suggest that exosomes are involved in many liver diseases including hepatitis C virus(HCV) infection, hepatitis B virus(HBV) infection, hepatocellualr carcinoma(HCC), liver fibrosis, cirrhosis, non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD). Moreover, exosomes are presented in nearly all human body fluids. Therefore, exosomal miRNA or proteins have the potential to be the novel biomarkers of liver diseases...
August 18, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Jeongeun Hyun, Jungwook Park, Sihyung Wang, Jieun Kim, Hyun-Hee Lee, Young-Su Seo, Youngmi Jung
Liver fibrosis is a major pathological feature of chronic liver diseases, including liver cancer. MicroRNAs (miRNAs), small noncoding RNAs, regulate gene expression posttranscriptionally and play important roles in various kinds of diseases; however, miRNA-associated hepatic fibrogenesis and its acting mechanisms are poorly investigated. Therefore, we performed an miRNA microarray in the fibrotic livers of Mus musculus treated with carbon-tetrachloride (CCl₄) and analyzed the biological functions engaged by the target genes of differentially-expressed miRNAs through gene ontology (GO) and in-depth pathway enrichment analysis...
2016: International Journal of Molecular Sciences
Ayano Takeuchi-Yorimoto, Yu Yamaura, Masayuki Kanki, Tetsuya Ide, Ayumi Nakata, Takahisa Noto, Masahiro Matsumoto
Evidence indicates that hepatic fibrosis is the initial lesion of cirrhosis or hepatocellular carcinoma in diseases such as nonalcoholic steatohepatitis (NASH). To induce NASH, we fed rats a choline-deficient and iron-supplemented L-amino acid-defined (CDAA) diet. Histopathological examination revealed that fibrosis appeared from week 4 and progressed to bridging fibrosis from week 12. Using qRT-PCR assays, we detected increased expression of miR-21, Mmp-9, and Timp-1 in liver that peaked during week 4, when fibrosis was first detected...
September 6, 2016: Toxicology Letters
Chao Yan, Li-Ping Shen, Rui Ma, Bo Li, Xiang-Yang Li, Hui Hua, Bo Zhang, Qian Yu, Yu-Gang Wang, Ren-Xian Tang, Kui-Yang Zheng
Clonorchis sinensis (C. sinensis) infection can lead to biliary fibrosis. MicroRNAs (miRNAs) play important roles in regulation of genes expression in the liver diseases. However, the differential expression of miRNAs that probably regulates the portal fibrogenesis caused by C. sinensis has not yet been investigated. Hepatic miRNAs expression profiles from C. sinensis-infected mice at different time-points were analyzed by miRNA microarray and validated by quantitative real-time PCR (qRT-PCR). 349 miRNAs were differentially expressed in the liver of the C...
September 2016: Infection, Genetics and Evolution
Kentaro Matsuura, Valeria De Giorgi, Cathy Schechterly, Richard Y Wang, Patrizia Farci, Yasuhito Tanaka, Harvey J Alter
UNLABELLED: The goal of this study was to determine whether an association exists between circulating microRNA (miRNA) levels and disease progression in chronic hepatitis C (CHC), whether plasma or extracellular vesicles (EVs) were optimal for miRNA measurement and their correlation with hepatic miRNA expression, and the mechanistic plausibility of this association. We studied 130 CHC patients prospectively followed over several decades. A comprehensive miRNA profile in plasma using microarray with 2578 probe sets showed 323 miRNAs differentially expressed between healthy individuals and CHC patients, but only six that distinguished patients with mild versus severe chronic hepatitis...
September 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Soo-Mi Kweon, Feng Chi, Reiichi Higashiyama, Keane Lai, Hidekazu Tsukamoto
PPAR-γ is essential for differentiation of hepatic stellate cells (HSC), and its loss due to epigenetic repression by methyl-CpG binding protein 2 (MeCP2) causes HSC myofibroblastic activation mediated in part via Wnt pathway, the key cellular event in liver fibrosis. Decreased miR-132 was previously proposed to promote MeCP2 protein translation for Ppar-γ repression in activated HSC (aHSC). The present study aimed to test this notion and to better understand the mechanisms of MeCP2 upregulation in aHSC. MeCP2 protein is increased on day 3 to 7 as HSC become activated in primary culture on plastic, but this is accompanied by increased but not reduced miR-132 or miR-212 which is also expected to target MeCP2 due to its similar sequence with miR-132...
2016: PloS One
Gianluigi Giannelli, Petra Koudelkova, Francesco Dituri, Wolfgang Mikulits
The epithelial to mesenchymal transition (EMT) is a multistep biological process whereby epithelial cells change in plasticity by transient de-differentiation into a mesenchymal phenotype. EMT and its reversal, mesenchymal to epithelial transition (MET), essentially occur during embryogenetic morphogenesis and have been increasingly described in fibrosis and cancer during the last decade. In carcinoma progression, EMT plays a crucial role in early steps of metastasis when cells lose cell-cell contacts due to ablation of E-cadherin and acquire increased motility to spread into surrounding or distant tissues...
October 2016: Journal of Hepatology
Delia Blaya, Mar Coll, Daniel Rodrigo-Torres, Maria Vila-Casadesús, José Altamirano, Marta Llopis, Isabel Graupera, Luis Perea, Beatriz Aguilar-Bravo, Alba Díaz, Jesus M Banales, Joan Clària, Juan José Lozano, Ramon Bataller, Juan Caballería, Pere Ginès, Pau Sancho-Bru
OBJECTIVE: MicroRNAs (miRNAs) are well-known regulators of disease pathogenesis and have great potential as biomarkers and therapeutic targets. We aimed at profiling miRNAs in alcoholic hepatitis (AH) and identifying miRNAs potentially involved in liver injury. DESIGN: MiRNA profiling was performed in liver samples from patients with AH, alcohol liver disease, non-alcoholic steatohepatitis, HCV disease and normal liver tissue. Expression of miRNAs was assessed in liver and serum from patients with AH and animal models...
September 2016: Gut
Chuanshan Zhang, Limin Wang, Tuergan Ali, Liang Li, Xiaojuan Bi, Junhua Wang, Guodong Lü, Yingmei Shao, Dominique A Vuitton, Hao Wen, Renyong Lin
BACKGROUND: Echinococcus granulosus infection causes cystic echinococcosis (CE); the generation of liver fibrosis around the parasitic larval cyst (metacestode) may play a major role in the spontaneous limitation of the parasitic growth; however, fibrogenesis has received little attention in CE. It has been reported that miR-19b plays a role in various diseases, including infectious diseases, by regulating fibrogenesis. However, its function in the development of liver fibrosis in E. granulosus infection is unknown...
2016: Parasites & Vectors
Simonetta Bandiera, Sophie Pernot, Hussein El Saghire, Sarah C Durand, Christine Thumann, Emilie Crouchet, Tao Ye, Isabel Fofana, Marine A Oudot, Jochen Barths, Catherine Schuster, Patrick Pessaux, Markus H Heim, Thomas F Baumert, Mirjam B Zeisel
UNLABELLED: Hepatitis C virus (HCV)-induced chronic liver disease is a leading cause of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCC development following chronic HCV infection remain poorly understood. MicroRNAs (miRNAs) play an important role in homeostasis within the liver, and deregulation of miRNAs has been associated with liver disease, including HCC. While host miRNAs are essential for HCV replication, viral infection in turn appears to induce alterations of intrahepatic miRNA networks...
July 15, 2016: Journal of Virology
Maoyao Wen, Ruoting Men, Xiaojing Liu, Li Yang
AIMS: This study aimed to determine the role of miR-30c in the process of hepatic stellate cells (HSCs) activation and liver fibrosis/cirrhosis and to explore the underlying mechanism. MAIN METHODS: A microarray analysis of miRNAs in HSCs was performed, and quantitative RT-PCR analyses were conducted to validate the results in HSCs, cirrhotic liver tissues and plasma. Rat HSCs were stimulated with angiotensin II (AngII) and transfected with miR-30c mimics/inhibitor to elucidate the underlying mechanism...
June 15, 2016: Life Sciences
Yoshiki Murakami, Norifumi Kawada
MicroRNAs (miRNAs) are a group of small non-coding RNAs that range in length from 20 to 25 nucleotides. miRNAs are specific for multiple cellular functions, including cell generation, differentiation, multiplication, carcinogenesis, and apoptosis. Many researchers have recently reported that the aberrant expression of miRNAs in hepatic tissue was related to the pathogenesis of liver disease, including viral hepatitis, hepatocellular carcinoma, and fatty liver disease. Multiple studies have proposed that an analysis of circulating miRNAs may be useful for diagnosing etiologies or staging the progression of liver disease, as well as for therapeutic purposes, e...
April 21, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Guojun Li, Jing Li, Changshui Li, Honggang Qi, Peihong Dong, Jianjian Zheng, Fujun Yu
BACKGROUND/AIMS: Emerging evidence shows that microRNAs (miRNAs) play a crucial role in the regulation of activation, proliferation and apoptosis of hepatic stellate cells (HSCs). Previous studies have indicated that miR-125a-5p is correlated with hepatitis B virus replication and disease progression. However, little is known about the biological role and underlying mechanism of miR-125a-5p in liver fibrosis. METHODS: We analyzed the level of miR-125a-5p in carbon tetrachloride-induced liver fibrosis and activated HSCs...
2016: Cellular Physiology and Biochemistry
Shelly C Lu, José M Mato, Cristina Espinosa-Diez, Santiago Lamas
The discovery of the microRNA (miRNA) family of small RNAs as fundamental regulators of post-transcriptional gene expression has fostered research on their importance in every area of biology and clinical medicine. In the particular area of liver metabolism and disease, miRNAs are gaining increasing importance. By focusing on two fundamental hepatic biosynthetic pathways, glutathione and methionine, we review recent advances on the comprehension of the role of miRNAs in liver pathophysiology and more specifically of models of hepatic cholestasis/fibrosis and hepatocellular carcinoma...
March 23, 2016: Free Radical Biology & Medicine
Chang Ho Lee, Ji Hyun Kim, Seong-Wook Lee
Hepatitis C virus (HCV) is a worldwide major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Accumulating evidence indicates that a number of microRNAs (miRNAs), which are able to exert an effect on liver biology and pathology, can regulate or be regulated by HCV infection. Many studies demonstrate that HCV utilizes host miRNAs and modulates expression of miRNAs in infected hepatocytes for its infection and propagation. In turn, host miRNAs can directly regulate HCV replication through interaction with the HCV RNA genome or by indirectly controlling the host pathways associated with the virus replication, which eventually induce HCV-related liver diseases such as liver fibrosis, hepatic cirrhosis, or HCC...
April 1, 2016: Current Drug Targets
Jeongeun Hyun, Sihyung Wang, Jieun Kim, Kummara Madhusudana Rao, Soo Yong Park, Ildoo Chung, Chang-Sik Ha, Sang-Woo Kim, Yang H Yun, Youngmi Jung
Hedgehog (Hh) signalling regulates hepatic fibrogenesis. MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver. MiRNA profiling shows that expression of miR-378 family members (miR-378a-3p, miR-378b and miR-378d) declines in carbon tetrachloride (CCl4)-treated compared with corn-oil-treated mice. Overexpression of miR-378a-3p, directly targeting Gli3 in activated hepatic stellate cells (HSCs), reduces expression of Gli3 and profibrotic genes but induces gfap, the inactivation marker of HSCs, in CCl4-treated liver...
2016: Nature Communications
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