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epithelial mesenchymal transition hepatocyte liver

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https://www.readbyqxmd.com/read/29758331/liver-regeneration-requires-yap1-tgf%C3%AE-dependent-epithelial-mesenchymal-transition-in-hepatocytes
#1
Seh-Hoon Oh, Marzena Swiderska-Syn, Mark L Jewell, Richard T Premont, Anna Mae Diehl
BACKGROUND: Chronic failure of mechanisms that promote effective regeneration of dead hepatocytes causes replacement of functional hepatic parenchyma with fibrous scar and ultimately results in cirrhosis. Therefore, defining and optimizing mechanisms that orchestrate effective regeneration might prevent cirrhosis. We hypothesized that effective regeneration of injured livers requires hepatocytes to evade the growth inhibitory actions of TGF-β since TGF-β signaling inhibits mature hepatocyte growth but drives cirrhosis pathogenesis...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29723851/transplantation-of-telocytes-attenuates-unilateral-ureter-obstruction-induced-renal-fibrosis-in-rats
#2
Long Zheng, Long Li, Guisheng Qi, Mushuang Hu, Chao Hu, Shuo Wang, Jiawei Li, Mingnan Zhang, Weitao Zhang, Yigang Zeng, Yi Zhang, Liping Li, Xuanchuan Wang, Miao Lin, Tongyu Zhu, Ruiming Rong
BACKGROUND/AIMS: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. METHODS: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days...
April 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29721169/differentiation-inducing-therapeutic-effect-of-notch-inhibition-in-reversing-malignant-transformation-of-liver-normal-stem-cells-via-met
#3
Hao Luo, Wei-Hui Liu, Hong-Yin Liang, Hong-Tao Yan, Ning Lin, Dong-Yu Li, Tao Wang, Li-Jun Tang
Background: Liver cancer stem cells (LCSCs) are the key factors for cancer metastasis, recurrent, and drug resistance. LCSCs are originated from either hepatocytes dedifferentiation or differentiation arresting of liver normal stem cells (LNSCs). Differentiation-inducing therapy is a novel strategy in solid tumors. Furthermore, Notch signaling pathway has been proved to play important role in the process of hepatocytes differentiation. In previous study, a malignant transformation cellular model of LNSCs has been built up, and in this study we are trying to illustrate whether inhibition of Notch can reverse this malignant tendency and drive these malignant cells back to differentiate into mature hepatocytes...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29678520/sorafenib-suppresses-tgf-%C3%AE-responses-by-inducing-caveolae-lipid-raft-mediated-internalization-degradation-of-cell-surface-type-ii-tgf-%C3%AE-receptors-implications-in-development-of-effective-adjunctive-therapy-for-hepatocellular-carcinoma
#4
Chih-Ling Chung, Shih-Wei Wang, Wei-Chih Sun, Chih-Wen Shu, Yu-Chen Kao, Meng-Shin Shiao, Chun-Lin Chen
Sorafenib is the only FDA approved drug for the treatment of advanced hepatocellular carcinoma (HCC) and other malignancies. Studies indicate that TGF-β signalling is associated with tumour progression in HCC. Autocrine and paracrine TGF-β promotes tumour growth and malignancy by inducing epithelial-mesenchymal transition (EMT). Sorafenib is believed to antagonize tumour progression by inhibiting TGF-β-induced EMT. It improves survival of patients but HCC later develops resistance and relapses. The underlying mechanism of resistance is unknown...
April 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29544731/autocrine-transforming-growth-factor-%C3%AE-activin-a-smad-signaling-induces-hepatic-progenitor-cells-undergoing-partial-epithelial-mesenchymal-transition-states
#5
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
May 2018: Biochimie
https://www.readbyqxmd.com/read/29497174/lack-of-hepatic-stimulator-substance-expression-promotes-hepatocellular-carcinoma-metastasis-partly-through-erk-activated-epithelial-mesenchymal-transition
#6
Xiao-Wei Jia, Zi-Wei Li, Ling-Yue Dong, Guang-Yong Sun, Xin Wang, Jian Gao, Yi-Peng Li, Yuan Wu, Wei An
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies due to its high frequency of metastasis via the epithelial-mesenchymal transition (EMT) pathway. Hepatic stimulator substance (HSS) can protect hepatocytes from injury and promote liver growth. Recent studies indicated that HSS expression is increased in HCC tissues; however, whether HSS expression is potentially associated with HCC metastasis, particularly through the EMT pathway, remains largely unknown. In this study, the relationship between HSS expression and HCC metastasis was investigated in clinical samples of HCC...
March 1, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29374697/effective-timing-of-surgical-resection-of-colorectal-cancer-liver-metastases-during-chemotherapy
#7
Shinji Osada, Ayana Gotoh, Ryoma Yokoi, Hiroshi Tsuchiya, Takuji Sakuratani, Yoshiyuki Sasaki, Naoki Okumura, Hideki Hayashi, Tsuyoshi Mukai
BACKGROUND/AIM: The aim of the present study was to further develop our previous study on c-Met expression in colorectal cancer and epithelial-mesenchymal transition (EMT) induced by hepatocyte growth factor (HGF), to investigate EMT in the process of liver metastases, and evaluate the effects of chemotherapy on EMT cells as a therapeutic strategy for colorectal liver metastasis. MATERIALS AND METHODS: CT26 colon cancer cells were treated with 5-FU and oxaliplatin with or without HGF...
February 2018: Anticancer Research
https://www.readbyqxmd.com/read/29356040/basolateral-cd147-induces-hepatocyte-polarity-loss-by-e-cadherin-ubiquitination-and-degradation-in-hepatocellular-carcinoma-progress
#8
Meng Lu, Jiao Wu, Zhi-Wei Hao, Yu-Kui Shang, Jing Xu, Gang Nan, Xia Li, Zhi-Nan Chen, Huijie Bian
Hepatocytes are epithelial cells with highly specialized polarity. The disorder and loss of hepatocyte polarity leads to a weakness of cell adhesion and connection, the induction of epithelial-mesenchymal transition, and eventually the occurrence of hepatocellular carcinoma (HCC). Cluster of differentiation 147 (CD147), a tumor-related glycoprotein, promotes epithelial-mesenchymal transition and the invasion of HCC. However, the function of CD147 in hepatocyte depolarization is unknown. Here we identified that CD147 was basolaterally polarized in hepatocyte membrane of liver tissues and HepG2 cells...
January 21, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29285255/agrin-para-secreted-by-pdgf-activated-human-hepatic-stellate-cells-promotes-hepatocarcinogenesis-in-vitro-and-in-vivo
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
January 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29026462/murine-hepatocellular-carcinoma-derived-stem-cells-reveal-epithelial-to-mesenchymal-plasticity
#15
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
#16
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
#17
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-remodeling-towards-regression-of-liver-fibrosis-novel-concepts
#18
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, together with 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)...
March 2018: 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
#19
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
#20
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
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