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epithelial mesenchymal transition hepatocyte liver

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https://www.readbyqxmd.com/read/29285255/agrin-para-secreted-by-pdgf-activated-human-hepatic-stellate-cells-promotes-hepatocarcinogenesis-in-vitro-and-in-vivo
#1
Xing Lv, Cheng Fang, Ruozhe Yin, Bowei Qiao, Runze Shang, Jianlin Wang, Wenjie Song, Yong He, Yong Chen
Evaluating the process and mechanism of fibrogenesis is essential in hepatocellular carcinoma (HCC), especially in hepatocyte transformation and oncogenic signaling. We evaluated the oncogenic role of agrin secreted by platelet-derived growth factor (PDGF)-induced hepatic stellate cell (HSC) in HCC. Cells were co-cultured to investigate the effect of activated HSC on hepatocytes. Liquid chromatography and protein profiling analysis were used to search the distinct proteins secreted in HSC supernatant. Sprague Dawley rats with Diethylnitrosamine (DEN)-induced HCC were used to simulate human liver cancer and sorafenib was administered to investigate its effect on hepatocarcinogenesis...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29238913/phthalazinone-pyrazole-enhances-the-hepatic-functions-of-human-embryonic-stem-cell-derived-hepatocyte-like-cells-via-suppression-of-the-epithelial-mesenchymal-transition
#2
Young-Jun Choi, Hyemin Kim, Ji-Woo Kim, Chang-Woo Song, Dae-Sung Kim, Seokjoo Yoon, Han-Jin Park
During liver development, nonpolarized hepatic progenitor cells differentiate into mature hepatocytes with distinct polarity. This polarity is essential for maintaining the intrinsic properties of hepatocytes. The balance between the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) plays a decisive role in differentiation of polarized hepatocytes. In this study, we found that phthalazinone pyrazole (PP), a selective inhibitor of Aurora-A kinase (Aurora-A), suppressed the EMT during the differentiation of hepatocyte-like cells (HLCs) from human embryonic stem cells...
December 13, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29211363/hierarchical-potential-differentiation-of-liver-cancer-stem-cells
#3
REVIEW
Wenfeng Zhang, Di Mu, Kai Feng
Hepatocellular carcinoma (HCC) is one of the most malignant tumors in Chinese people and offers poor prognosis. Tumor tissue, like normal tissue, is hierarchically differentiated. Thus, minor tumor cell populations able to differentiate, such as stem cells, sustain tumor self-renewal and proliferation. The fact that liver cancer stem cells (CSCs) with different surface markers appear heterogeneous with respect to oncogenesis and drug resistance indicates that subpopulations of surface markers preserve the hierarchical potential of differentiation during proliferation, deterioration and relapse...
October 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29187885/huaier-restrains-proliferative-and-migratory-potential-of-hepatocellular-carcinoma-cells-partially-through-decreased-yes-associated-protein-1
#4
Liang Shan, Yan Li, Hongyuan Jiang, Yuquan Tao, Zijun Qian, Lan Li, Feng Cai, Lifang Ma, Yongchun Yu
In China, Trametes robiniophila Murr (Huaier), a traditional Chinese herbal medicine, has been widely used in adjuvant therapies of hepatocellular carcinoma (HCC). However, the molecular mechanisms have not been fully understood. The aims of this study are to investigate the functions and mechanisms of Huaier on inhibiting proliferation and migration of HCC cells. Firstly, cell counting kit-8 (CCK-8) and colony formation shown Huaier inhibited proliferation of HCC Bel-7404, Bel-7402 and SMMC-7721 cells in a dose-dependent manner, and this inhibition might be due to Huaier decreased the expressions of the proliferating cell nuclear antigen (PCNA), the nuclear proliferation related antigen (Ki-67) and CyclinD1 detected by western blotting analysis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29170436/fate-tracing-of-hepatocytes-in-mouse-liver
#5
Xiaowen Gu, Danyi Huang, Lei Ci, Jiahao Shi, Mengjie Zhang, Hua Yang, Zhugang Wang, Zhejin Sheng, Ruilin Sun, Jian Fei
Hepatocytes perform most of the functions of the liver and are considered terminally differentiated cells. Recently, it has been suggested that hepatocytes might have the potential to transdifferentiate or dedifferentiate under physiological or pathological conditions in vivo. Epithelial-mesenchymal transition of hepatocytes in liver fibrosis has also been proposed. However, these findings have not been fully confirmed. In this study, hepatocytes were genetically labelled for cell fate tracing using lacZ via the tamoxifen-induced CreERT/loxP system...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29128616/di-n-octylphthalate-acts-as-a-proliferative-agent-in-murine-cell-hepatocytes-by-regulating-the-levels-of-tgf-%C3%AE-and-pro-apoptotic-proteins
#6
Shelby L Buckner, Allison N Pruitt, Cecilia N Thomas, Monisha Y Amin, Laurence L Miller, Faith E Wiley, Maria Eugenia Sabbatini
Di-n-octylphthalate (DNOP) is a phthalate used in the manufacturing of a wide variety of polyvinyl chloride-containing medical and consumer products. A study on chronic exposure to DNOP in rodents showed the development of pre-neoplastic hepatic lesions following exposure to a tumor initiator. The objective of this study was to identify the mechanisms by which DNOP leads to pre-neoplastic hepatic lesions. Mouse hepatocyte AML-12 and FL83B cells were treated with DNOP. The rate of cell proliferation was increased in treated cells in a concentration-dependent manner...
November 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29026462/murine-hepatocellular-carcinoma-derived-stem-cells-reveal-epithelial-to-mesenchymal-plasticity
#7
Aparna Jayachandran, Ritu Shrestha, Bijay Dhungel, I-Tao Huang, Marianna Yumi Kawashima Vasconcelos, Brian J Morrison, Charmaine A Ramlogan-Steel, Jason C Steel
AIM: To establish a model to enrich and characterize stem-like cells from murine normal liver and hepatocellular carcinoma (HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesenchymal transition (EMT). METHODS: In this study, we utilized a stem cell conditioned serum-free medium to enrich stem-like cells from mouse HCC and normal liver cell lines, Hepa 1-6 and AML12, respectively. We isolated the 3-dimensional spheres and assessed their stemness characteristics by evaluating the RNA levels of stemness genes and a cell surface stem cell marker by quantitative reverse transcriptase-PCR (qRT-PCR)...
September 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/29025375/dopamine-induced-sult1a3-4-promotes-emt-and-cancer-stemness-in-hepatocellular-carcinoma
#8
Juan Zou, Hong Li, Qianling Huang, Xiaomin Liu, Xiaoxiao Qi, Ying Wang, Linlin Lu, Zhongqiu Liu
Hepatocellular carcinoma has the second highest incidence rate among malignant cancers in China. Hepatocellular carcinoma development is complex because of the metabolism disequilibrium involving SULT1A3/4, a predominant sulfotransferase that metabolizes sulfonic xenobiotics and endogenous catecholamines. However, the correlation between SULT1A3/4 and hepatocellular carcinoma progression is unclear. By utilizing immunofluorescence and immunohistochemical analysis, we found that in nine hepatocellular carcinoma clinical specimens, SULT1A3/4 was abundantly expressed in tumor tissues compared to that in the adjacent tissues...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28918026/anti-fibrotic-effects-of-synthetic-oligodeoxynucleotide-for-tgf-%C3%AE-1-and-smad-in-an-animal-model-of-liver-cirrhosis
#9
Jung-Yeon Kim, Hyun-Jin An, Woon-Hae Kim, Mi-Gyeong Gwon, Hyemin Gu, Yoon-Yub Park, Kwan-Kyu Park
Liver fibrosis is characterized by changes in tissue architecture and extracellular matrix composition. Liver fibrosis affects not only hepatocytes but also the non-parenchymal cells such as hepatic stellate cells (HSCs), which are essential for maintaining an intact liver structure and function. Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that induces liver fibrosis through activation of Smad signaling pathways. To improve a new therapeutic approach, synthetic TGF-β1/Smad oligodeoxynucleotide (ODN) was used to suppress both TGF-β1 expression and Smad transcription factor using a combination of antisense ODN and decoy ODN...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28895372/-tipping-extracellular-matrix-remodelling-towards-regression-of-liver-fibrosis-novel-concepts
#10
Fernando Magdaleno, Robert Schierwagen, Frank E Uschner, Jonel Trebicka
Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, as well as other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC)...
September 11, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28821798/unconventional-mapk-gsk-3%C3%AE-pathway-behind-atypical-epithelial-mesenchymal-transition-in-hepatocellular-carcinoma
#11
Sana Parveen, Dhiviya Vedagiri, Hitha Gopalan Nair, Haripriya Parthasarathy, Krishnan Harinivas Harshan
We recently reported an atypical epithelial mesenchymal transition (EMT) in human hepatoma cell culture Huh7.5, which was non-responsive to the canonical EMT-transcription factors. Here we characterize major pathways regulating this atypical EMT through whole genome transcriptome profiling and molecular analysis, and identify a unique regulation of EMT by GSK-3β. Our analysis reveals remarkable suppression of several key liver-specific markers in Huh7.5M cells indicating that EMT not only changes the epithelial properties, but alters the characteristics associated with hepatocytes as well...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#12
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 a previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition (EMT) state 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 an HCV core-expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28765687/can-a-fibrotic-liver-afford-epithelial-mesenchymal-transition
#13
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
#14
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...
November 9, 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
#15
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
#16
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
#17
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...
August 28, 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
#18
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
#19
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
#20
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
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