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Functional analysis of the cytoprotective transcription factor Nrf2 in skin morphogenesis and disease: Identification of Nrf2 target genes

ABSTRACT: The Nrf2 transcription factor is a key player in the cellular stress response, which regulates the expression of important antioxidant enzymes and other cytoprotective proteins. We recently generated a novel transgenic mouse model to determine the function of Nrf2 in the skin. These mice revealed interesting phenotypic abnormalities, including hyperkeratosis and acanthosis. To gain insight into the underlying molecular mechanisms, we wanted to identify genes, which are differentially expressed in the skin of wild-type and mutant mice before the onset of phenotypic abnormalities.

ORGANISM(S): Mus musculus

PROVIDER: GSE35160 | GEO | 2012/02/01

SECONDARY ACCESSION(S): PRJNA150787

REPOSITORIES: GEO

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Functional analysis of the cytoprotective transcription factor Nrf2 in skin morphogenesis and disease: Identification of Nrf2 target genes

Project description:The Nrf2 transcription factor is a key player in the cellular stress response, which regulates the expression of important antioxidant enzymes and other cytoprotective proteins. We recently generated a novel transgenic mouse model to determine the function of Nrf2 in the skin. These mice revealed interesting phenotypic abnormalities, including hyperkeratosis and acanthosis. To gain insight into the underlying molecular mechanisms, we wanted to identify genes, which are differentially expressed in the skin of wild-type and mutant mice before the onset of phenotypic abnormalities. RNA from whole skin of 3 single P2.5 K5cre-caNrf2 (tg/tg) and 3 single P2.5 K5cre-wt (tg/wt=control) mice were used

2012-02-01 | E-GEOD-35160 | biostudies-arrayexpress

Functional analysis of the cytoprotective transcription factor Nrf2 in keratinocytes: Identification of Nrf2-regulated miRNAs

Project description:Nrf2-regulated mRNAs are known; however, no Nrf2-regulated miRs have been identified miR microarray analysis from total RNA samples was performed to test which miRs are regulated by Nrf2 Total RNA from skin of mice with constitutively active Nrf2 (CMV-caNrf2), dominant-negative Nrf2 (dnNrf2), and correcponding control littermates (K5Cre(wt) for CMV-caNrf2 and wt for dnNrf2)

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Comparison of P18 mouse epidermis from K5-FGFR1/FGFR2 knockout and wild-type mice

Project description:Fibroblast growth factors (FGFs) are master regulators of organogenesis and tissue homeostasis. We generated FGF receptor (FGFR)-deficient mice to unravel their functions in the skin. These mice revealed interesting phenotypic abnormalities, including loss of skin appendages, cutaneous inflammation, keratinocyte hyperproliferation, and acanthosis. To gain insight into the underlying molecular mechanisms, we wanted to identify genes, which are differentially expressed in the skin of wild-type and mutant mice before the onset of phenotypic alterations.

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Differentially regulated miRNAs in skin fibroblasts with constitutively active Nrf2

Project description:The NRF2 transcription factor is a key regulator of the cellular antioxidant response, and pharmacological NRF2 activation is a promising strategy for the prevention of age-related diseases. Here we show, however, that genetic activation of Nrf2 in skin fibroblasts leads to the production of a matrisome, which is similar to aged skin and characterized by reduced synthesis and deposition of selected matrix proteins, including the major skin collagens. Mechanistically, the production of an aging matrisome results from Nrf2-mediated overexpression of microRNAs (miRs), which directly suppress collagen expression independently of myofibroblast differentiation. This is functionally important, as Nrf2 activation in fibroblasts caused structural abnormalities of the dermal ECM and increased the susceptibility to skin tearing, similar to aged skin. Activation of endogenous NRF2 was observed in human skin from elderly individuals in vitro and in vivo. These data implicate a key role for activated NRF2 in controlling age-related molecular and biomechanical skin alterations.

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Functional analysis of the cytoprotective transcription factor Nrf2 in keratinocytes: Identification of Nrf2-regulated miRNAs

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Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus

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Lactobacilli modulate epithelial cytoprotection through the Nrf2 pathway [Microarray]

2015-09-01 | GSE72553 | GEO

Lactobacilli modulate epithelial cytoprotection through the Nrf2 pathway [RNA-Seq]

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Lactobacilli modulate epithelial cytoprotection through the Nrf2 pathway [RNA-Seq]

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