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epithelial mesenchymal transition hepatocyte liver

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https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#1
Young-Chan Kwon, Reina Sasaki, Keith Meyer, Ranjit Ray
Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In our previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition state (EMT) and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of HCV core expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28765687/can-a-fibrotic-liver-afford-epithelial-mesenchymal-transition
#2
EDITORIAL
Stefan Munker, Yong-Le Wu, Hui-Guo Ding, Roman Liebe, Hong-Lei Weng
The question whether epithelial-mesenchymal transition (EMT) occurs during liver fibrogenesis is a controversial issue. In vitro studies confirm that hepatocytes or cholangiocytes undergo EMT upon transforming growth factor β (TGF-β) stimulation, whereas in vivo experiments based on genetic fate mapping of specific cell populations suggest that EMT does not occur in fibrotic animal models. In this review we present current data supporting or opposing EMT in chronic liver disease and discuss conditions for the occurrence of EMT in patients...
July 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28692045/impact-of-histone-demethylase-kdm3a-dependent-ap-1-transactivity-on-hepatotumorigenesis-induced-by-pi3k-activation
#3
T Nakatsuka, K Tateishi, Y Kudo, K Yamamoto, H Nakagawa, H Fujiwara, R Takahashi, K Miyabayashi, Y Asaoka, Y Tanaka, H Ijichi, Y Hirata, M Otsuka, M Kato, J Sakai, M Tachibana, H Aburatani, Y Shinkai, K Koike
Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28684878/hepatocyte-nuclear-factor-1beta-enhances-the-stemness-of-hepatocellular-carcinoma-cells-through-activation-of-the-notch-pathway
#4
Jing-Ni Zhu, Lu Jiang, Jing-Hua Jiang, Xue Yang, Xiao-Yong Li, Jian-Xin Zeng, Rong-Yu Shi, Yang Shi, Xiao-Rong Pan, Zhi-Peng Han, Li-Xin Wei
Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28624456/in%C3%A2-vitro-evidences-of-epithelial-to-mesenchymal-transition-in-low-cell-density-cultured-human-fetal-hepatocytes
#5
Cinzia Maria Chinnici, Vitale Miceli, Mariangela Pampalone, Antonio Lo Nigro, Giandomenico Amico, Pier Giulio Conaldi
Culturing fetal hepatocytes in high cell-density allowed stabilization of the hepatocyte phenotype up to 8 weeks, including the maintenance of liver-specific functions. On the other hand, when cultured at low cell-density, fetal hepatocytes underwent morphological modifications and acquired fibroblastic morphology. Since a switch from E-cadherin to vimentin expression accompanied these changes, we hypothesized the occurrence of epithelial-to-mesenchymal transition when fetal hepatocytes were cultured at low cell-density...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28536011/tg737-regulates-epithelial-mesenchymal-transition-and-cancer-stem%C3%A2-cell-properties-via-a-negative-feedback-circuit-between-snail-and%C3%A2-hnf4%C3%AE-during-liver-stem-cell-malignant-transformation
#6
Qike Huang, Meng Pu, Ge Zhao, Bin Dai, Zhenyuan Bian, Haili Tang, Chong Chen, Wei Liu, Xuan Qu, Liangliang Shen, Kaishan Tao
Determining the origin of liver cancer stem cells is important for treating hepatocellular carcinoma. Tg737 deficiency plays an important role in the malignant transformation of liver stem cells, but the underlying mechanism remains unclear. Here we established a chemical-induced mouse hepatoma model and found that Tg737 and hepatocyte nuclear factor 4-alpha (HNF4α) expression decreased and epithelial-mesenchymal transition (EMT)-related marker expression increased during liver cancer development. To investigate the underlying mechanism, we knocked down Tg737 in WB-F344 (WB) rat hepatic oval cells...
May 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28500745/advanced-oxidation-protein-products-induce-hepatocyte-epithelial-mesenchymal-transition-via-a-ros-dependent-tgf-%C3%AE-smad-signaling-pathway
#7
Shibo Sun, Fang Xie, Qifan Zhang, Zhonglin Cui, Xinsheng Cheng, Feng Zhong, Kun He, Jie Zhou
Epithelial-mesenchymal transition (EMT) occurs during the progression of liver fibrosis in response to chronic liver injury. However, the molecular mechanism underlying the regulation of hepatocyte EMT remains unclear. The aim of this study was to determine whether advanced oxidation protein products (AOPP) had an effect on hepatocyte EMT. The human L02 hepatocyte cell line and hepatocytes from normal Sprague-Dawley rats were challenged with AOPP treatment in both in vitro and in vivo studies. The expression of cell and molecular markers of EMT in L02 hepatocytes were studied using Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays...
May 13, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28465351/an-hnf4%C3%AE-microrna-194-192-signaling-axis-maintains-hepatic-cell-function
#8
Aoi Morimoto, Mana Kannari, Yuichi Tsuchida, Shota Sasaki, Chinatsu Saito, Tsuyoshi Matsuta, Tsukasa Maeda, Megumi Akiyama, Takahiro Nakamura, Masakiyo Sakaguchi, Nobukazu Nameki, Frank J Gonzalez, Yusuke Inoue
Hepatocyte nuclear factor 4α (HNF4α) controls the expression of liver-specific protein-coding genes. However, some microRNAs are also modulated by HNF4α, and it is not known whether they are direct targets of HNF4α and whether they influence hepatic function. In this study, we found that HNF4α regulates microRNAs, indicated by marked down-regulation of miR-194 and miR-192 (miR-194/192) in liver-specific Hnf4a-null (Hnf4a(ΔH)) mice. Transactivation of the shared miR-194/192 promoter was dependent on HNF4α expression, indicating that miR-194/192 is a target gene of HNF4α...
June 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28458469/tm4sf5-mediated-roles-in-the-development-of-fibrotic-phenotypes
#9
REVIEW
Jihye Ryu, Jung Weon Lee
Transmembrane 4 L six family member 5 (TM4SF5) can form tetraspanin-enriched microdomains (TERMs) on the cell's surface. TERMs contain protein-protein complexes comprised of tetraspanins, growth factor receptors, and integrins. These complexes regulate communication between extracellular and intracellular spaces to control diverse cellular functions. TM4SF5 influences the epithelial-mesenchymal transition (EMT), aberrant multilayer cellular growth, drug resistance, enhanced migration and invasion, circulation through the bloodstream, tumor-initiation property, metastasis, and muscle development in zebrafish...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28406452/suppression-of-hepatic-epithelial-to-mesenchymal-transition-by-melittin-via-blocking-of-tgf%C3%AE-smad-and-mapk-jnk-signaling-pathways
#10
Ji-Hyun Park, Byoungduck Park, Kwan-Kyu Park
Transforming growth factor (TGF)-β1 plays a crucial role in the epithelial-to-mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC), which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a major component of bee venom and is effective in rheumatoid arthritis, pain relief, cancer cell proliferation, fibrosis and immune modulating activity. In this study, we found that MEL inhibits hepatic EMT in vitro and in vivo, regulating the TGFβ/Smad and TGFβ/nonSmad signaling pathways...
April 13, 2017: Toxins
https://www.readbyqxmd.com/read/28336518/bmp-9-interferes-with-liver-regeneration-and-promotes-liver-fibrosis
#11
Katja Breitkopf-Heinlein, Christoph Meyer, Courtney König, Haristi Gaitantzi, Annalisa Addante, Maria Thomas, Eliza Wiercinska, Chen Cai, Qi Li, Fengqi Wan, Claus Hellerbrand, Nektarios A Valous, Maximilian Hahnel, Christian Ehlting, Johannes G Bode, Stephanie Müller-Bohl, Ursula Klingmüller, Jutta Altenöder, Iryna Ilkavets, Marie-José Goumans, Lukas J A C Hawinkels, Se-Jin Lee, Matthias Wieland, Carolin Mogler, Matthias P Ebert, Blanca Herrera, Hellmut Augustin, Aránzazu Sánchez, Steven Dooley, Peter Ten Dijke
OBJECTIVE: Bone morphogenetic protein (BMP)-9, a member of the transforming growth factor-β family of cytokines, is constitutively produced in the liver. Systemic levels act on many organs and tissues including bone and endothelium, but little is known about its hepatic functions in health and disease. DESIGN: Levels of BMP-9 and its receptors were analysed in primary liver cells. Direct effects of BMP-9 on hepatic stellate cells (HSCs) and hepatocytes were studied in vitro, and the role of BMP-9 was examined in acute and chronic liver injury models in mice...
May 2017: Gut
https://www.readbyqxmd.com/read/28088733/long-non-coding-rna-uc001kfo-promotes-hepatocellular-carcinoma-proliferation-and-metastasis-by-targeting-%C3%AE-sma
#12
Yanfeng Pan, Tao Qin, Shenglu Yin, Xianqiang Zhang, Xiaojuan Gao, Lifen Mu
Several long non-coding RNAs (lncRNAs) have been investigated and found to be correlated with the behaviours and prognosis of hepatocellular carcinoma (HCC); Specifically, we revealed that the lncRNA UC001kfo was differentially expressed in HCC tissues compared with normal liver tissues using lncRNA microarrays, but its functional role in cancers, including HCC, has not yet been elucidated. The present study found that the expression of UC001kfo was upregulated in HCC tissues and cell lines in comparison with tumour-adjacent tissues and normal hepatocytes, respectively...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27911878/y-box-binding-protein-1-promotes-hepatocellular-carcinoma-initiating-cell-progression-and-tumorigenesis-via-wnt-%C3%AE-catenin-pathway
#13
Hsiao-Mei Chao, Hong-Xuan Huang, Po-Hsiang Chang, Kuo-Chang Tseng, Atsushi Miyajima, Edward Chern
Y-box binding protein-1 (YB-1) is a pleiotropic molecule that binds DNA to regulate genes on a transcriptional level in the nucleus and binds RNA to modulate gene translation in the cytoplasm. In our previous studies, YB-1 was also characterized as a fetal hepatic protein that regulates the maturation of hepatocytes and is upregulated during liver regeneration. Moreover, YB-1 has been shown to be expressed in human hepatocellular carcinoma (HCC). However, the role of YB-1 in HCC remains unclear. Here, we aimed to characterize the role of YB-1 in HCC...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27881141/analysis-of-epithelial-mesenchymal-transition-markers-in-the-histogenesis-of-hepatic-progenitor-cell-in-hbv-related-liver-diseases
#14
Wei Xu, Nong-Rong Wang, Hua-Feng Wang, Qiong Feng, Jun Deng, Zhi-Qiang Gong, Jian Sun, Xiao-Liang Lou, Xue-Feng Yu, Lv Zhou, Jin-Ping Hu, Xiao-Feng Huang, Xiao-Qing Qi, Yan-Juan Deng, Rui Gong, Yan Guo, Meng-Meng Wang, Jia-Cheng Xiao, Huan Deng
BACKGROUND: The origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs. METHODS: Surgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection...
November 24, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27878730/mesenchymal-epithelial-transition-in-culture-of-stromal-progenitor-cells-isolated-from-the-liver-of-a-patient-with-alcoholic-cirrhosis
#15
I V Kholodenko, R V Kholodenko, G V Manukyan, V V Burunova, K N Yarygin
The cells isolated from biopsy specimen of a patient with alcoholic liver cirrhosis and cultured under standard conditions for obtaining stromal cell culture clearly diverged during early passages into two morphologically and phenotypically different subtypes: epithelial and mesenchymal. Mesenchymal cells expressed CD90 and CD44 and epithelial cells expressed CD166, CD227, and hepatocyte growth factor receptor Met. Starting from passage 6, the culture underwent spontaneous morphological changes and by passages 8-10 contained only epithelium-like cells...
November 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27876854/mir-706-inhibits-the-oxidative-stress-induced-activation-of-pkc%C3%AE-taok1-in-liver-fibrogenesis
#16
Ruili Yin, Duo Guo, Shuxian Zhang, Xiuying Zhang
Oxidative stress induces the activation of liver fibrogenic cells (myofibroblasts), thus promoting the expression of fibrosis-related genes, leading to hepatic fibrogenesis. MicroRNAs (miRNAs) are a new class of small RNAs ~18-25 nucleotides in length involved in post-transcriptional regulation of gene expression. Wound-healing and remodeling processes in liver fibrosis have been associated with changes in hepatic miRNA expression. However, the role of miR-706 in liver fibrogenesis is currently unknown. In the present study, we show that miR-706 is abundantly expressed in hepatocytes...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27791279/rar-related-orphan-receptor-gamma-ror-%C3%AE-mediates-epithelial-mesenchymal-transition-of-hepatocytes-during-hepatic-fibrosis
#17
Sung Min Kim, Jung Eun Choi, Wonhee Hur, Jung-Hee Kim, Sung Woo Hong, Eun Byul Lee, Joon Ho Lee, Tian Zhu Li, Pil Soo Sung, Seung Kew Yoon
The epithelial-mesenchymal transition (EMT) is involved in many different types of cellular behavior, including liver fibrosis. In this report, we studied a novel function of RAR-related orphan receptor gamma (ROR-γ) in hepatocyte EMT during liver fibrosis. To induce EMT in vitro, primary hepatocytes and FL83B cells were treated with TGF-β1. Expression of ROR-γ was analyzed by Western blot in the fibrotic mouse livers and human livers with cirrhosis. To verify the role of ROR-γ in hepatocyte EMT, we silenced ROR-γ in FL83B cells using a lentiviral short hairpin RNA (shRNA) vector...
August 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27784427/-expression-of-sal-like-4-in-primary-hepatocellular-carcinoma-and-its-association-with-epithelial-mesenchymal-transition
#18
J Xu, J Wang, Y Hu, X X Wang, L L Cheng, H Y Yu
Objective: To investigate the expression of sal-like 4 (SALL4) in tissues of primary hepatocellular carcinoma (HCC) and its association with epithelial-mesenchymal transition (EMT) and clinicopathological characteristics. Methods: Immunohistochemistry and nucleic acid in situ hybridization were used to measure the mRNA expression of SALL4, epithelial cadherin (E-cadherin), vimentin, and Snail in 72 HCC samples, 2 fetal liver samples, and 2 normal adult liver tissue samples. Results: Strong expression of SALL4 was observed in hepatoblasts in fetal liver, but SALL4 expression was not observed in primitive hematopoietic cells and normal adult hepatocytes or biliary epithelial cells...
July 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27662828/generation-and-characterization-of-a-novel-transgenic-mouse-harboring-conditional-nuclear-factor-kappa-b-rela-knockout-alleles
#19
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...
September 23, 2016: BMC Developmental Biology
https://www.readbyqxmd.com/read/27606718/design-and-construction-of-a-multi-organ-microfluidic-chip-mimicking-the-in-vivo-microenvironment-of-lung-cancer-metastasis
#20
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
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