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Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia [neutrophils]

ABSTRACT: The transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs. These studies tested the role of Nrf2 during pneumonia induced by Streptococcus pneumoniae (SP) at 24 hours in mice and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils.

ORGANISM(S): Mus musculus

PROVIDER: GSE83613 | GEO | 2016/09/09

SECONDARY ACCESSION(S): PRJNA326565

REPOSITORIES: GEO

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Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia [whole lung]

Project description:The transcription factor Nrf2 (gene symbol Nfe2l2) regulates the transcriptional response to oxidative stress and plays a critical protective role in the lungs. These studies tested the role of Nrf2 during pneumonia induced by Streptococcus pneumoniae (SP) at 24 hours in mice and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils.

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Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia

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Analysis of NFE2L2 (NRF2) binding to chromatin in primary human keratinocytes

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Project description:The pediatric liver cancer hepatoblastoma (HB) often expresses mutant forms of b-catenin and dysregulates the Hippo tumor suppressor pathway. Murine HBs can be generated by co-expressing b-catenin mutants and the constitutively active Hippo effector YAPS127A. Some human HBs also express mutant forms of NFE2L2/NRF2 (NFE2L2), a bHLH transcription factor that tempers oxidative and electrophilic stress. In doing so, NFE2L2 either suppresses or facilitates tumorigenesis in a context- and time-dependent manner. We show here that two patient-derived NFE2L2 missense mutants, L30P and R34P, markedly accelerate HB growth in association with diffuse cyst formation, an otherwise uncommon feature of human HB. Surprisingly, we found that any two members of the mutant b-catenin-YAPS127A-L30P/R34P triad were tumorigenic, thus providing direct evidence for NFE2L2’s oncogenicity. Each tumor group showed distinct features but shared a similarly deregulated set of 22 transcripts, 10 of which perfectly correlated with survival in human HBs. 17 transcripts also correlated with survival in multiple cancers. One of the most deregulated transcripts encoded Serpin E1, a serine protease inhibitor with roles in fibrinolysis, tumor growth and extracellular matrix formation. The combination of mutant b-catenin-YAPS127A-Serpin E1 neither accelerated tumor growth nor generated cysts but did promote large-scale necrosis that was often associated with the cysts seen in mutant b-catenin-YAPS127A-L30P/R34P tumor, albeit on a lesser scale. These findings establish the direct oncogencity of NFE2L2 mutants and identify key transcripts, including Serpin E1, that impact tumor growth and other HB features.

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Leukocyte kinetics and bacterial clearance during S. pneumoniae pneumonia and contributions of ICAM-1

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Gene expression profiling of neutrophils and whole lung tissue from wildtype and Nrf2 null (Nfe2l2-/-) mice during S. pneumoniae pneumonia

Project description:This SuperSeries is composed of the SubSeries listed below.

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