共查询到20条相似文献,搜索用时 31 毫秒
1.
Wei Gao Ping Zhou Xiaocui Ma Benjamin Tschudy-Seney Jiamei Chen Nataly L. Magner Alexander Revzin Jan A. Nolta Mark A. Zern Yuyou Duan 《PloS one》2014,9(11)
Background
Alcohol insult triggers complex events in the liver, promoting fibrogenic/inflammatory signals and in more advanced cases, aberrant matrix deposition. It is well accepted that the regenerative capacity of the adult liver is impaired during alcohol injury. The liver progenitor/stem cells have been shown to play an important role in liver regeneration -in response to various chronic injuries; however, the effects of alcohol on stem cell differentiation in the liver are not well understood.Methods
We employed hepatic progenitor cells derived from hESCs to study the impact of ethanol on hepatocyte differentiation by exposure of these progenitor cells to ethanol during hepatocyte differentiation.Results
We found that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitor cells in a dose-dependent manner. There was also a moderate cell cycle arrest at G1/S checkpoint in the ethanol treated cells, which is associated with a reduced level of cyclin D1 in these cells. Ethanol treatment specifically inhibited the activation of the ERK but not JNK nor the p38 MAP signaling pathway. At the same time, the WNT signaling pathway was also reduced in the cells exposed to ethanol. Upon evaluating the effects of the inhibitors of these two signaling pathways, we determined that the Erk inhibitor replicated the effects of ethanol on the hepatocyte differentiation and attenuated the WNT/β-catenin signaling, however, inhibitors of WNT only partially replicated the effects of ethanol on the hepatocyte differentiation.Conclusion
Our results demonstrated that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitors through inhibiting the MAPK/ERK signaling pathway, and subsequently attenuating the WNT signaling pathway. Thus, our finding provides a novel insight into the mechanism by which alcohol regulates cell fate selection of hESC-derived hepatic progenitor cells, and the identified pathways may provide therapeutic targets aimed at promoting liver repair and regeneration during alcoholic injury. 相似文献2.
Jiang W Couroucli XI Wang L Barrios R Moorthy B 《Biochemical and biophysical research communications》2011,(1):79-85
Background/aims
TEC, a member of the TEC family of non-receptor type protein tyrosine kinases, has recently been suggested to play a role in hepatocyte proliferation and liver regeneration. This study aims to investigate the putative mechanisms of TEC kinase regulation of hepatocyte differentiation, i.e. to explore which signaling pathway TEC is involved in, and how TEC is activated in hepatocyte after hepatectomy and hepatocyte growth factor (HGF) stimulation.Methods
We performed immunoprecipitation (IP) and immunoblotting (IB) to examine TEC tyrosine phosphorylation after partial hepatectomy in mice and HGF stimulation in WB F-344 hepatic cells. The TEC kinase activity was determined by in vitro kinase assay. Reporter gene assay, antisense oligonucleotide and TEC dominant negative mutant (TECKM) were used to examine the possible signaling pathways in which TEC is involved. The cell proliferation rate was evaluated by 3H-TdR incorporation.Results
TEC phosphorylation and kinase activity were increased in 1 h after hepatectomy or HGF treatment. TEC enhanced the activity of Elk and serum response element (SRE). Inhibition of MEK1 suppressed TEC phosphorylation. Blocking TEC activity dramatically decreased the activation of Erk. Reduced TEC kinase activity also suppressed the proliferation of WB F-344 cells. These results suggest TEC is involved in the Ras-MAPK pathway and acts between MEK1 and Erk.Conclusions
TEC promotes hepatocyte proliferation and regeneration and is involved in HGF-induced Erk signaling pathway. 相似文献3.
Babu?A?Manjasetty Frank?H?Niesen Christoph?Scheich Yvette?Roske Frank?Goetz Joachim?Behlke Volker?Sievert Udo?Heinemann
Background
Human Aortic Preferentially Expressed Protein-1 (APEG-1) is a novel specific smooth muscle differentiation marker thought to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). 相似文献4.
Background
MicroRNAs are a class of small regulatory RNAs that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism and proliferation. This study aims to explore the effect of miR-34a in hepatocyte proliferation and its potential role in liver regeneration termination.Methodology/Principal Finding
MiR-34a was highly induced after partial hepatectomy. Overexpression of miR-34a in BRL-3A cells could significantly inhibit cell proliferation and down-regulate the expression of inhibin βB (INHBB) and Met. In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay. More importantly, INHBB siRNA significantly repressed cell proliferation. A decrease of INHBB and Met was detected in regenerating liver.Conclusion/Significance
MiR-34a expression was upregulated during the late phase of liver regeneration. MiR-34a-mediated regulation of INHBB and Met may collectively contribute to the suppression of hepatocyte proliferation. 相似文献5.
Background
The mechanism involved in the maintenance and differentiation of embryonic stem (ES) cells is incompletely understood. 相似文献6.
Tatjana?P?Stromskaya Ekaterina?Y?Rybalkina Tatjana?N?Zabotina Alexander?A?Shishkin Alla?A?Stavrovskaya
Background
Multidrug resistance (MDR) phenotype of malignant cells is the major problem in the chemotherapy of neoplasia. The treatment of leukemia with retinoids is aimed on the induction of leukemic cells differentiation. However the interconnections between retinoid regulated differentiation of leukemic cells and regulation of MDR remains unclear. 相似文献7.
Grahame Mckenzie George Ward Yvette Stallwood Emmanuel Briend Sofia Papadia Andrew Lennard Martin Turner Brian Champion Giles E Hardingham 《BMC cell biology》2006,7(1):10-11
Background
Notch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways. 相似文献8.
Anne-Katrin Giese Jana Frahm Rayk Hübner Jiankai Luo Andreas Wree Moritz J Frech Arndt Rolfs Stefanie Ortinau 《BMC cell biology》2010,11(1):94
Background
Hypoxia plays a critical role in various cellular mechanisms, including proliferation and differentiation of neural stem and progenitor cells. In the present study, we explored the impact of lowered oxygen on the differentiation potential of human neural progenitor cells, and the role of erythropoietin in the differentiation process. 相似文献9.
Cell-extracellular matrix interactions regulate neural differentiation of human embryonic stem cells
Wu Ma Tara Tavakoli Eric Derby Yevgeniya Serebryakova Mahendra S Rao Mark P Mattson 《BMC developmental biology》2008,8(1):90
Background
Interactions of cells with the extracellular matrix (ECM) are critical for the establishment and maintenance of stem cell self-renewal and differentiation. However, the ECM is a complex mixture of matrix molecules; little is known about the role of ECM components in human embryonic stem cell (hESC) differentiation into neural progenitors and neurons. 相似文献10.
Fang Tan Samit Ghosh Flaubert Mbeunkui Robert Thomas Joshua A Weiner Solomon F Ofori-Acquah 《BMC molecular biology》2010,11(1):91
Background
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. However, its role in hematopoietic differentiation has not previously been defined. 相似文献11.
Background
Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited. 相似文献12.
Background
Connective Tissue Growth Factor (CTGF/CCN2), a known matrix-associated protein, is required for the lactogenic differentiation of mouse mammary epithelial cells. An HC11 mammary epithelial cell line expressing CTGF/CCN2 was constructed to dissect the cellular responses to CTGF/CCN2 that contribute to this differentiation program. 相似文献13.
Differential expression of WNT4 in testicular and ovarian development in a marsupial 总被引:1,自引:0,他引:1
Background
WNT4 is a key regulator of gonadal differentiation in humans and mice, playing a pivotal role in early embryogenesis. Using a marsupial, the tammar wallaby, in which most gonadal differentiation occurs after birth whilst the young is in the pouch, we show by quantitative PCR during early testicular and ovarian development that WNT4 is differentially expressed ingonads. 相似文献14.
Background
During early differentiation of Dictyostelium the attractant cAMP is released periodically to induce aggregation of the cells. Here we pursue the question whether pulsatile cAMP signaling is coupled to a basic Ca2+-oscillation. 相似文献15.
Anna Pistocchi Germano Gaudenzi Silvia Carra Erica Bresciani Luca Del Giacco Franco Cotelli 《BMC developmental biology》2008,8(1):27
Background
Prox1, the vertebrate homolog of prospero in Drosophila melanogaster, is a divergent homeogene that regulates cell proliferation, fate determination and differentiation during vertebrate embryonic development. 相似文献16.
Background
Cell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability. 相似文献17.
Sarah Snykers Tamara Vanhaecke Ann De Becker Peggy Papeleu Mathieu Vinken Ivan Van Riet Vera Rogiers 《BMC developmental biology》2007,7(1):24
Background
The capability of human mesenchymal stem cells (hMSC) derived of adult bone marrow to undergo in vitro hepatic differentiation was investigated. 相似文献18.
Peter Ghosh Jiehua Wu Susan Shimmon Andrew CW Zannettino Stan Gronthos Silviu Itescu 《Arthritis research & therapy》2010,12(1):R28
Introduction
This study was undertaken to determine whether the anti-osteoarthritis drug pentosan polysulfate (PPS) influenced mesenchymal precursor cell (MPC) proliferation and differentiation. 相似文献19.
Bhaskar?Bhattacharya Jingli?Cai Youngquan?Luo Takumi?Miura Josef?Mejido Sandii?N?Brimble Xianmin?Zeng Thomas?C?Schulz Mahendra?S?Rao Raj?K?Puri