RGD Reference Report - Epidermal hyperplasia induced by Raf-MAPK signaling requires Stat3 activation. - Rat Genome Database

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Epidermal hyperplasia induced by Raf-MAPK signaling requires Stat3 activation.

Authors: Tarutani, M  Nakajima, K  Takaishi, M  Ohko, K  Sano, S 
Citation: Tarutani M, etal., J Dermatol Sci. 2013 Nov;72(2):110-5. doi: 10.1016/j.jdermsci.2013.06.007. Epub 2013 Jun 21.
RGD ID: 8699499
Pubmed: PMID:23870655   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jdermsci.2013.06.007   (Journal Full-text)

BACKGROUND: Raf is one of the downstream effectors of Ras GTPases, and plays a key role in regulating cell proliferation and differentiation through the activation of MAPK. We have previously demonstrated that temporal induction of Raf in the epidermis of K14-Raf:ER transgenic mice results in epidermal hyperplasia resembling squamous cell carcinoma and psoriasis. It has been demonstrated that epidermal Stat3 activation is required for psoriasis development, since keratinocyte-specific Stat3 activation in a mouse model elicits a psoriasis-like phenotype, which is reversed by inhibition of Stat3 signaling. OBJECTIVE: The aim of this study was whether Stat3 signaling is involved in Raf-MAPK-dependent epidermal hyperplasia. METHODS: K14-Raf:ER transgenic mice, in which the 4-hydroxytamoxifen (4OHT)-responsive mutant estrogen receptor ligand binding domain-Raf fusion gene is expressed under control of the keratin 14 promoter, were mated with epidermis-specific Stat3 null mice (K5-Cre.Stat3(flox/flox)). K5-Cre.Stat3(flox/flox) mice were used to define the impact of Stat3 deficiency on Raf-induced epidermal hyperplasia. RESULTS: Over-expression of Raf by 4OHT treatment in K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice greatly attenuated the epidermal hyperplasia and dermal cell infiltrates compared with K14-Raf:ER;K5-Cre.Stat3(flox/WT) mice. Also, up-regulation of psoriasis-associated cytokine profiles, including VEGF, was inhibited in the skin from K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice following 4OHT treatment. CONCLUSION: These results clearly indicate that Raf-MAPK-dependent psoriatic-like epidermal hyperplasia requires Stat3 signaling in keratinocytes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Epidermal Hyperplasia  ISOStat3 (Mus musculus)8699499; 8699499 RGD 
Epidermal Hyperplasia  IMP 8699499 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Stat3  (signal transducer and activator of transcription 3)

Genes (Mus musculus)
Stat3  (signal transducer and activator of transcription 3)

Genes (Homo sapiens)
STAT3  (signal transducer and activator of transcription 3)


Additional Information