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epithelial mesenchymal transition hepatocyte liver

Talha Ijaz, Maki Wakamiya, Hong Sun, Adrian Recinos, Ronald G Tilton, Allan R Brasier
BACKGROUND: Nuclear Factor-Kappa B (NF-kB) is a family of transcription factors that are important in embryonic development, inflammation, epithelial-to-mesenchymal transition and cancer. The 65 kDa RelA subunit is the major transcriptional activator of the NF-kB pathways. Whole-body deficiency of RelA leads to massive apoptosis of liver hepatocytes and death in utero. To study the role of RelA in physiology and in disease states in a manner that circumvents this embryonic lethal phenotype, we have generated a mouse with RelA conditional knockout (CKO) alleles containing loxP sites that are deleted by activated Cre recombinase...
2016: BMC Developmental Biology
Zhiyun Xu, Encheng Li, Zhe Guo, Ruofei Yu, Hualong Hao, Yitong Xu, Zhao Sun, Xiancheng Li, Jianxin Lyu, Qi Wang
Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels...
October 5, 2016: ACS Applied Materials & Interfaces
Norio Kubo, Kenichiro Araki, Hiroyuki Kuwano, Ken Shirabe
The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines...
August 14, 2016: World Journal of Gastroenterology: WJG
Shaffer R S Mok, Sachin Mohan, Navjot Grewal, Adam B Elfant, Thomas A Judge
BACKGROUND: Biphenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC) is an uncommon primary liver neoplasm. Due to limitations in radiologic imaging for the diagnosis of this condition, biopsy is a common method for diagnosis, which is invasive and holds potential complications. To identify alternative means for obtaining the diagnosis and assessing the prognosis of this condition, we evaluated biomarkers for biphenotypic HCC-CC using a genetic database. METHODS: To evaluate the genetic associations with each variable we utilized GeneCards(®), The Human Gene Compendium (http://www...
August 2016: Journal of Gastrointestinal Oncology
Tian Zhu Li, Sung Min Kim, Wonhee Hur, Jung Eun Choi, Jung-Hee Kim, Sung Woo Hong, Eun Byul Lee, Joon Ho Lee, Seung Kew Yoon
Background/Aims: The role of Elk-3 in the epithelial-mesenchymal transition (EMT) during liver fibrogenesis remains unclear. Here, we determined the expression of Elk-3 in in vitro and in vivo models and in human liver fibrotic tissues. We also investigated the molecular relationships among Elk-3, early growth response-1 (Egr-1), and the mitogen activated protein kinases (MAPK) pathway during EMT in hepatocytes. Methods: We established an in vitro EMT model in which normal mouse hepatocyte cell lines were treated with transforming growth factor (TGF)-β1 and a CCl4-induced liver fibrosis model...
August 19, 2016: Gut and Liver
Ioanna Vallianou, Dimitra Dafou, Niki Vassilaki, Penelope Mavromara, Margarita Hadzopoulou-Cladaras
Hepatitis C Virus (HCV) infection presents with a disturbed lipid profile and can evolve to hepatic steatosis and hepatocellular carcinoma (HCC). Hepatocyte Nuclear Factor 4 alpha (HNF4α) is the most abundant transcription factor in the liver, a key regulator of hepatic lipid metabolism and a critical determinant of Epithelial to Mesenchymal Transition and hepatic development. We have previously shown that transient inhibition of HNF4α initiates transformation of immortalized hepatocytes through a feedback loop consisting of miR-24, IL6 receptor (IL6R), STAT3, miR-124 and miR-629, suggesting a central role of HNF4α in HCC...
September 2016: International Journal of Biochemistry & Cell Biology
Li-Li Zhang, Shan Huang, Xiao-Xin Ma, Wen-Yong Zhang, Dan Wang, Si-Yi Jin, Yan-Ping Zhang, Yang Li, Xu Li
Epithelial-mesenchymal transition (EMT) is correlated with NAPDH oxidase (NOX)-derived reactive oxygen species (ROS). The ROS-induced NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a novel mechanism of EMT. Angiotensin II (AngII) induces EMT by regulating intracellular ROS. Nevertheless, it has not been reported whether AngII could induce hepatocyte EMT. Angiotensin-(1-7) [Ang-(1-7)] can inhibit the effects of AngII via a counter-regulatory mechanism. However, whether Ang-(1-7) attenuated the effects of AngII on hepatocyte EMT remains unclear...
August 2016: Free Radical Biology & Medicine
Qisheng Li, Catherine Sodroski, Brianna Lowey, Cameron J Schweitzer, Helen Cha, Fang Zhang, T Jake Liang
Hepatitis C virus (HCV) enters the host cell through interactions with a cascade of cellular factors. Although significant progress has been made in understanding HCV entry, the precise mechanisms by which HCV exploits the receptor complex and host machinery to enter the cell remain unclear. This intricate process of viral entry likely depends on additional yet-to-be-defined cellular molecules. Recently, by applying integrative functional genomics approaches, we identified and interrogated distinct sets of host dependencies in the complete HCV life cycle...
July 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Orit Goldman, Victor Julian Valdes, Elena Ezhkova, Valerie Gouon-Evans
Epithelial-mesenchymal transition (EMT) and the mesenchymal-epithelial transition (MET) are processes required for embryo organogenesis. Liver develops from the epithelial foregut endoderm from which the liver progenitors, hepatoblasts, are specified. The migrating hepatoblasts acquire a mesenchymal phenotype to form the liver bud. In mid-gestation, hepatoblasts mature into epithelial structures: the hepatocyte cords and biliary ducts. While EMT has been associated with liver bud formation, nothing is known about its contribution to hepatic specification...
July 2016: Stem Cell Research
Kaiming Wu, Changhong Ye, Lin Lin, Yimin Chu, Meng Ji, Weiping Dai, Xin Zeng, Yong Lin
MicroRNA-21 (miR-21) has emerged as a critical regulatory molecule and an important serum marker in hepatic fibrogenesis. The aim of the present study was to investigate the role of inhibiting miR-21 on hepatic fibrosis treatment. Serum miR-21 levels in 60 healthy individuals and 180 patients with different stages of liver cirrhosis were examined, miR-21 levels in normal or cirrhotic human liver tissues (n=10 each) were also detected. An adenoviral vector (Ad-TuD-21) carrying the sponging ToughDecoy (TuD)-RNA sequence against miR-21 was constructed to reduce miR-21 expression efficiently in vitro and in vivo Histological and immunohistological examinations were performed to evaluate the inhibitory effects and mechanism of Ad-TuD-21 delivery into carbon tetrachloride (CCl4) induced hepatic fibrosis rats by targeting extracellular signal-regulated kinase 1 (ERK1) signalling in hepatic stellate cells (HSC) and hepatocyte epithelial-mesenchymal transition (EMT)...
August 1, 2016: Clinical Science (1979-)
Wen-Guang Zhang, Chuan-Fei Li, Min Liu, Xiao-Feng Chen, Kai Shuai, Xin Kong, Lin Lv, Zhe-Chuan Mei
Aquaporin 9 (AQP9) is the main aquaglyceroporin in the liver. Few studies have been performed regarding the role of AQP9 in hepatocellular carcinoma (HCC). Here, we report the expression and function of AQP9 in HCC tissues and cell lines. We found that AQP9 mRNA and protein levels were down-regulated in HCC tissues and human hepatoma cell lines compared to the para-cancer normal liver tissues and normal hepatocyte line, respectively. In a human HCC SMMC-7721 cell line, over-expression of AQP9 suppressed cell invasion in vitro and xenograft tumor growth in vivo...
May 20, 2016: Cancer Letters
Sihem Mebarki, Romain Désert, Laurent Sulpice, Marie Sicard, Mireille Desille, Frédéric Canal, Hélène Dubois-Pot Schneider, Damien Bergeat, Bruno Turlin, Pascale Bellaud, Elise Lavergne, Rémy Le Guével, Anne Corlu, Christine Perret, Cédric Coulouarn, Bruno Clément, Orlando Musso
About 20% hepatocellular carcinomas (HCCs) display wild-type β-catenin, enhanced Wnt signaling, hepatocyte dedifferentiation and bad outcome, suggesting a specific impact of Wnt signals on HCC stem/progenitor cells. To study Wnt-specific molecular pathways, cell fates and clinical outcome, we fine-tuned Wnt/β-catenin signaling in liver progenitor cells, using the prototypical Wnt ligand Wnt3a. Cell biology assays and transcriptomic profiling were performed in HepaRG hepatic progenitors exposed to Wnt3a after β-catenin knockdown or Wnt inhibition with FZD8_CRD...
May 13, 2016: Oncotarget
Nirajan Shrestha, Lokendra Chand, Myung Kwan Han, Seung Ok Lee, Chan Young Kim, Yeon Jun Jeong
Glutamine, traditionally a non-essential amino acid, now has been considered as essential in serious illness and injury. It is a major precursor for glutathione synthesis. However, the anti-fibrotic effect of glutamine and its molecular mechanism in experimental liver fibrosis have not been explored. In the present study we aimed to examine the potential role of glutamine in carbon tetrachloride (CCl4) induced liver fibrosis and TGF-β1 mediated epithelial mesenchymal transition (EMT) and apoptosis in mouse hepatocytes...
July 2016: Food and Chemical Toxicology
Ana Belen Fajardo-Puerta, Mireia Mato Prado, Adam E Frampton, Long R Jiao
Hepatocyte growth factor (HGF) is a multifunctional cytokine with important roles in cell proliferation, survival, motility and morphogenesis. Secreted by cells of mesenchymal origin, HGF is the specific ligand for the tyrosine-kinase receptor c-MET (cellular mesenchymal-epithelial transition), also called MET, which is expressed in different types of epithelial, endothelial and haematopoietic progenitor cells. The HGF/MET axis is involved in several biological processes, such as embryogenesis, organogenesis, adult tissue regeneration (including wound healing and liver regeneration) and carcinogenesis, for both solid and haematological malignancies...
July 2016: Journal of Clinical Pathology
Mona M Zoheiry, Shaimaa Aa Hasan, Eman El-Ahwany, Faten M Nagy, Hoda Abu Taleb, Mona Nosseir, Mona Magdy, Safa Meshaal, Mohamed Darwish El-Talkawy, Inas Raafat
INTRODUCTION: Hepatitis C virus (HCV) is a major cause of chronic liver disease in Egypt, leading to hepatic fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM). Newly-recognized pathogenic mechanisms point to the epithelial-mesenchymal transition (EMT) of hepatocytes to matrix synthesizing (myo-) fibroblasts. Transforming growth factor-beta (TGF-β1), bone morphogenic protein (BMP)-7, and connective tissue growth factor (CTGF) are biomarkers reflecting the EMT process...
December 2015: Electronic Physician
Yayi He, Yan Wang, Theresa Boyle, Shengxiang Ren, Dan Chan, Chris Rivard, Xuefei Li, Jiayu Li, Caicun Zhou, Fred R Hirsch
BACKGROUND: Hepatocyte growth factor (HGF)-mediated mesenchymal-to-epithelial transition factor (MET) gene amplification is a common mechanism for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). MET gene amplification has also been associated with hepatic metastases in patients with lung cancer. The aim of this study was to investigate whether hepatic metastases are associated with decreased efficacy of erlotinib in patients with adenocarcinoma...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Shigetsugu Takano, Maximilian Reichert, Basil Bakir, Koushik K Das, Takahiro Nishida, Masaru Miyazaki, Steffen Heeg, Meredith A Collins, Benoît Marchand, Philip D Hicks, Anirban Maitra, Anil K Rustgi
The two major isoforms of the paired-related homeodomain transcription factor 1 (Prrx1), Prrx1a and Prrx1b, are involved in pancreatic development, pancreatitis, and carcinogenesis, although the biological role that these isoforms serve in the systemic dissemination of pancreatic ductal adenocarcinoma (PDAC) has not been investigated. An epithelial-mesenchymal transition (EMT) is believed to be important for primary tumor progression and dissemination, whereas a mesenchymal-epithelial transition (MET) appears crucial for metastatic colonization...
January 15, 2016: Genes & Development
Miki Nishio, Keishi Sugimachi, Hiroki Goto, Jia Wang, Takumi Morikawa, Yosuke Miyachi, Yusuke Takano, Hiroki Hikasa, Tohru Itoh, Satoshi O Suzuki, Hiroki Kurihara, Shinichi Aishima, Andrew Leask, Takehiko Sasaki, Toru Nakano, Hiroshi Nishina, Yuji Nishikawa, Yoshitaka Sekido, Kazuwa Nakao, Kazuo Shin-Ya, Koshi Mimori, Akira Suzuki
Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway that coactivate large tumor suppressor homolog (LATS) kinases. Mob1a/1b double deficiency in mouse liver (LMob1DKO) results in hyperplasia of oval cells and immature cholangiocytes accompanied by inflammatory cell infiltration and fibrosis. More than half of mutant mice die within 3 wk of birth. All survivors eventually develop liver cancers, particularly combined hepatocellular and cholangiocarcinomas (cHC-CCs) and intrahepatic cholangiocellular carcinomas (ICCs), and die by age 60 wk...
January 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jennifer H Benbow, Kyle J Thompson, Heidi L Cope, Elizabeth Brandon-Warner, Catherine R Culberson, Krista L Bossi, Ting Li, Mark W Russo, Keith S Gersin, Iain H McKillop, Andrew S deLemos, Laura W Schrum
Obesity is an independent risk factor for the development of liver fibrosis/cirrhosis and hepatocellular carcinoma (HCC). Tenascin-C (TnC), an extracellular matrix protein, is transiently expressed during tissue injury and plays a role in fibrogenesis and tumorigenesis. However, the mechanistic role of TnC signaling in the development of HCC remains unknown. We developed a diet-induced obesity HCC mouse model and examined TnC expression and liver injury. To determine the cellular mechanism of TnC signaling in promoting inflammation and hepatocyte epithelial-mesenchymal transition and migration, we used primary hepatocytes and hepatoma and macrophage cell lines...
January 2016: American Journal of Pathology
Malena Manzi, María L Bacigalupo, Pablo Carabias, María T Elola, Carlota Wolfenstein-Todel, Gabriel A Rabinovich, María V Espelt, María F Troncoso
Galectin-1 (Gal1), a β-galactoside-binding protein elevated in hepatocellular carcinoma (HCC), promotes epithelial-mesenchymal transition (EMT) and its expression correlates with HCC growth, invasiveness, and metastasis. During the early stages of HCC, transforming growth factor β1 (TGF-β1 ) acts as a tumor suppressor; however in advanced stages, HCC cells lose their cytostatic response to TGF-β1 and undergo EMT. Here, we investigated the role of Gal1 on liver endothelial cell biology, and the interplay between Gal1 and TGF-β1 in HCC progression...
July 2016: Journal of Cellular Physiology
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