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Microarray gene expression profiling of transgenic mice with myocardium-specific expression of RKIP or a GRK-specific peptide inhibitor

ABSTRACT: The Raf kinase inhibitor protein (RKIP) is a dual inhibitor of the Raf kinase and the G-protein-coupled receptor kinase 2 (GRK2). GRK2 is an indispensable kinase, which exerts a major role in the pathogenesis of heart failure, and inhibition of GRK2 is cardioprotective in experimental models of heart failure. To investigate the cardiac function of RKIP as GRK2 inhibitor, we generated transgenic mice with myocardium-specific expression of RKIP under control of the alpha-MHC promoter. For comparison, mice with myocardium-specific expression of a GRK-specific peptide inhibitor (GRK-Inh) were also generated. Two different transgenic mouse models were established. Transgenic RKIP mice and transgenic GRK-Inh mice were born at Mendelian frequencey and grew to adulthood normally.

ORGANISM(S): Mus musculus

PROVIDER: GSE42753 | GEO | 2012/12/06

SECONDARY ACCESSION(S): PRJNA183014

REPOSITORIES: GEO

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Microarray gene expression profiling of transgenic mice with myocardium-specific expression of RKIP or a GRK-specific peptide inhibitor

Project description:The Raf kinase inhibitor protein (RKIP) is a dual inhibitor of the Raf kinase and the G-protein-coupled receptor kinase 2 (GRK2). GRK2 is an indispensable kinase, which exerts a major role in the pathogenesis of heart failure, and inhibition of GRK2 is cardioprotective in experimental models of heart failure. To investigate the cardiac function of RKIP as GRK2 inhibitor, we generated transgenic mice with myocardium-specific expression of RKIP under control of the alpha-MHC promoter. For comparison, mice with myocardium-specific expression of a GRK-specific peptide inhibitor (GRK-Inh) were also generated. Two different transgenic mouse models were established. Transgenic RKIP mice and transgenic GRK-Inh mice were born at Mendelian frequencey and grew to adulthood normally. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) RKIP-transgenic mice, (ii) GRK-Inh-transgenic mice, and (iii) B6 control mice.

2012-12-06 | E-GEOD-42753 | biostudies-arrayexpress

Whole genome cardiac gene expression profiling of transgenic mice with myocardium-specific expression of RKIP (PEBP1), kinase-inactive GRK2-K220R (ADRBK1-K220R), SCD1, and UCP1

Project description:The raf kinase inhibitor protein, RKIP, is up-regulated on cadiac biopsy specimens of heart failure patients. To investigate the in vivo role of an increased cardiac content of RKIP, we generated transgenic mice with myocardium-specific expression of RKIP (PEBP1; phosphatidylethanolamine binding protein 1) under control of the alpha-MHC promoter in B6 (C57BL/6J) background. Because RKIP is a dual-specific GRK2 and Raf kinase inhibitor, RKIP-transgenic mice were compared to transgenic mice with myocardium-specific expression of the GRK2 inhibitor, GRK2-K220R, which is a kinase-inactive GRK2 (ADRBK1) mutant with dominant-negative function. In frame of our studies, we found that RKIP-transgenic mice developed signs of heart failure and cardiotoxic lipid load at an age of 8 months. In contrast, transgenic expression of GRK2-K220R improved cardiac function and protected against chronic pressure overload-induced symptoms of heart failure. To identify genes related to cardiotoxic lipid load, we further determined the cardiac gene expression profile of Tg-SCD1 mice with mypcardium-specific expression of SCD1 (stearoyl-CoA desaturase-1) and Tg-UCP1 mice with heart-specific expression of UCP1 (uncoupling protein 1).

2018-09-18 | GSE120020 | GEO

Cardiac transcriptome analysis of RKIP-transgenic and GRK2-transgenic mice by NGS

Project description:The RAF kinase inhibitor protein, RKIP, is a dual inhibitor of the RAF1 kinase and the G-protein-coupled receptor kinase 2 (GRK2). By inhibition of the proto-oncogenic and pro-survival RAF1-MAPK pathway, the RAF kinase inhibitor protein, RKIP, acts as a tumor suppressor, which enhances cardiomyocyte death and promotes the development of symptoms of heart failure. To elucidate pathomechanisms of heart failure induced by RKIP, the study determined the cardiac transcriptomes of eight-month-old, male, transgenic mice with cardiac-specific expression of RKIP (PEBP1) under control of the myocardium-specific, alpha-MHC promoter. In addition, the study determined the cardiac transcriptomes of GRK2-transgenic mice. Tg-GRK2 mice have a slightly increased transgenic expression of GRK2. According to NGS data, cardiac GRK2-Grk2 transcript levels of Tg-GRK2 mice are 1.59±0.10-fold higher than those of non-transgenic FVB hearts. In Tg-GRK2 mice, transgenic GRK2 is expressed under control of the ubiquitous CMV immediate-early promoter/enhancer. The non-transgenic control group are age-matched, male, nontransgenic FVB/N mice. NGS data of this study document transcriptome changes underlying the heart failure phenotype induced by transgenic RKIP expression and cardiac degeneration induced by GRK2 expression.

2021-12-27 | GSE191316 | GEO

LFQ of mouse brain in ischemic stroke

Project description:Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are part of the Raf/MEK/ERK1/2 cascade and are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. Therefore, this study aimed to investigate the impact of ERK1/2 after cerebral ischemia using transgenic mice with ubiquitous overexpression of ERK2 or of the Raf kinase inhibitor protein (RKIP), an inhibitor of the ERK1/2 signaling cascade.

2022-02-17 | PXD030067 | Pride

Effect of knockdown of RKIP(=PEBP1) on gene expression in mouse breast cancer cells

Project description:Raf-1 kinase inhibitor protein (RKIP = PEBP1) has been shown to negatively regulate signaling pathways including the MAPK and NFkappaB pathways involved in cancer progression and metastasis. RKIP acts as a suppressor of metastasis, but the exact mechanisms are unclear. In this study, knockdown of RKIP expression was used to identify the targets of RKIP expression. GSEA analysis identified interferon response genes as downregulated in the RKIP knockdown cells.

2022-07-21 | GSE206259 | GEO

Mus musculus

Project description:Microarray gene expression profiling of transgenic mice with myocardium-specific expression of RKIP or a GRK-specific peptide inhibitor

| PRJNA183014 | ENA

Gene expression data from 1833 cells expressing RKIP vs control

Project description:RKIP regulates human breast tumor metastasis. We use gene expression array analysis to identify genes regulated by RKIP in human breast cancer cells. Total RNAs were extracted from 1833 cells expressing mutant RKIP (S153E-RKIP, a more potent Raf-1 inhibitor) and vector control. Affymetrix GeneChip hgu133plus2.0 Arrays were performed to detail the gene expression and identify the genes regulated by RKIP in human breast cancer cells.

2014-07-01 | E-GEOD-47378 | biostudies-arrayexpress

Cardiac transcriptome analysis of RKIP-transgenic and GRK2-transgenic mice by NGS

Project description:Cardiac transcriptome analysis of RKIP-transgenic and GRK2-transgenic mice by NGS

| PRJNA790970 | ENA

Whole genome cardiac gene expression profiling of transgenic mice with myocardium-specific expression of RKIP (PEBP1), kinase-inactive GRK2-K220R (ADRBK1-K220R), SCD1, and UCP1

Project description:Whole genome cardiac gene expression profiling of transgenic mice with myocardium-specific expression of RKIP (PEBP1), kinase-inactive GRK2-K220R (ADRBK1-K220R), SCD1, and UCP1

| PRJNA491406 | ENA

RKIP regulates differentiation-related features in melanocytic cells

Project description:Raf Kinase Inhibitor Protein (RKIP) has been extensively reported as an inhibitor of key signaling pathways involved in the aggressive tumor phenotype and shows decreased expression in several types of cancers. However, little is known about RKIP in melanoma or regarding its function in normal cells. We examined the role of RKIP in both primary melanocytes and malignant melanoma cells and evaluated its diagnostic and prognostic value. IHC analysis revealed a significantly higher expression of RKIP in nevi compared with early-stage (stage I-II, AJCC 8th) melanoma biopsies. Proliferation, wound healing, and collagen-coated transwell assays uncovered the implication of RKIP on the motility but not on the proliferative capacity of melanoma cells as RKIP protein levels were inversely correlated with the migration capacity of both primary and metastatic melanoma cells but did not alter other parameters. As shown by RNA sequencing, endogenous RKIP knockdown in primary melanocytes triggered the deregulation of cellular differentiation-related processes, including genes (i.e., ZEB1, THY-1) closely related to the EMT. Interestingly, NANOG was identified as a putative transcriptional regulator of many of the deregulated genes, and RKIP was able to decrease the activation of the NANOG promoter. As a whole, our data support the utility of RKIP as a diagnostic marker for early-stage melanomas. In addition, these findings indicate its participation in the maintenance of a differentiated state of melanocytic cells by modulating genes intimately linked to the cellular motility and explain the progressive decrease of RKIP often described in tumors.

2020-07-01 | GSE151585 | GEO

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