Glucose regulates RMI1 expression through the E2F pathways in adipose cells

Suwa, Akira; Yoshino, Masayasu; Kurama, Takeshi; Shimokawa, Teruhiko; Aramori, Ichiro

doi:10.1007/s12020-011-9455-4

Cited by 4 publications

(3 citation statements)

References 18 publications

(29 reference statements)

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“…Loss of RecQ-mediated genome instability 1 (RMI1) inhibits E2F8 expression 78, Knockdown of E2f8 suppresses this glucose inducing up-regulation of RMI1 expression 77. RMI1 and E2F8 consist of a feedback machinery to regulate energy balance in adipose tissue through modulating preadipocyte proliferation.…”

Section: E2f8 and Diseasesmentioning

confidence: 99%

E2F8 is a Potential Therapeutic Target for Hepatocellular Carcinoma

Xiao

Liu

et al. 2017

J. Cancer

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E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development via activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization. It also involves closely a variety of cellular physiological functions and pathological processes, which may bring a new breakthrough for the treatment of certain diseases, especially the HCC. Here, we summarize the latest progress of E2F8 on its relevant functions and mechanisms as well as potential application.

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Section: E2f8 and Diseasesmentioning

confidence: 99%

E2F8 is a Potential Therapeutic Target for Hepatocellular Carcinoma

Xiao

Liu

et al. 2017

J. Cancer

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“…A screen for essential adipogenic genes is important to discover novel therapeutic targets for obesity. Hyperplasia and hypertrophy of adipose cells greatly increases the risk of developing cardiovascular disease [9] , [60] , [61] . Due to the central role of adipocyte hyperplasia in the pathogenesis of obesity, discovering genes which inhibit or induce adipogenesis provides important drug and therapeutic targets and the OP9-K line will expedite these discoveries.…”

Section: Discussionmentioning

confidence: 99%

Development of an OP9 Derived Cell Line as a Robust Model to Rapidly Study Adipocyte Differentiation

et al. 2014

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One hallmark of obesity is adipocyte hypertrophy and hyperplasia. To gain novel insights into adipose biology and therapeutics, there is a pressing need for a robust, rapid, and informative cell model of adipocyte differentiation for potential RNAi and drug screens. Current models are prohibitive for drug and RNAi screens due to a slow differentiation time course and resistance to transfection. We asked if we could create a rapid, robust model of adipogenesis to potentially enable rapid functional and obesity therapeutic screens. We generated the clonal population OP9-K, which differentiates rapidly and reproducibly, and displays classic adipocyte morphology: rounded cell shape, lipid accumulation, and coalescence of lipids into a large droplet. We further validate the OP9-K cells as an adipocyte model system by microarray analysis of the differentiating transcriptome. OP9-K differentiates via known adipogenic pathways, involving the transcriptional activation and repression of common adipose markers Plin1, Gata2, C/Ebpα and C/Ebpβ and biological pathways, such as lipid metabolism, PPARγ signaling, and osteogenesis. We implemented a method to quantify lipid accumulation using automated microscopy and tested the ability of our model to detect alterations in lipid accumulation by reducing levels of the known master adipogenic regulator Pparγ. We further utilized our model to query the effects of a novel obesity therapeutic target, the transcription factor SPI1. We determine that reduction in levels of Spi1 leads to an increase in lipid accumulation. We demonstrate rapid, robust differentiation and efficient transfectability of the OP9-K cell model of adipogenesis. Together with our microscopy based lipid accumulation assay, adipogenesis assays can be achieved in just four days' time. The results of this study can contribute to the development of rapid screens with the potential to deepen our understanding of adipose biology and efficiently test obesity therapeutics.

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“…Initially, E2F5 was considered a transcription suppressor in cell proliferation studies ( Gaubatz et al, 2000 ; Chen et al, 2009 ) and to be related to fatty acid metabolism ( Urs et al, 2004 ). E2F5 is expressed in human and mouse adipocytes ( Urs et al, 2004 ; Suwa et al, 2011 ); however, its role in adipogenesis remains unknown. Krüppel-like factor 7 ( KLF7 ) is associated with obesity, type II diabetes, and cardiovascular and cerebrovascular diseases ( Zhang et al, 2013 ; Makeeva et al, 2015 ; Wang et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%