RGD Reference Report - Stat3 as a therapeutic target for the treatment of psoriasis: a clinical feasibility study with STA-21, a Stat3 inhibitor. - Rat Genome Database

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Stat3 as a therapeutic target for the treatment of psoriasis: a clinical feasibility study with STA-21, a Stat3 inhibitor.

Authors: Miyoshi, K  Takaishi, M  Nakajima, K  Ikeda, M  Kanda, T  Tarutani, M  Iiyama, T  Asao, N  DiGiovanni, J  Sano, S 
Citation: Miyoshi K, etal., J Invest Dermatol. 2011 Jan;131(1):108-17. doi: 10.1038/jid.2010.255. Epub 2010 Sep 2.
RGD ID: 8694306
Pubmed: PMID:20811392   (View Abstract at PubMed)
DOI: DOI:10.1038/jid.2010.255   (Journal Full-text)

Epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3, and increased levels of cytokines and growth factors that promote Stat3 activation have been found within psoriatic lesions. K5.Stat3C transgenic mice, in which keratinocytes express a constitutively active Stat3, develop psoriasis-like skin lesions. In this study, we examined whether STA-21, a small Stat3 inhibitor, could be useful in ameliorating the skin lesions not only in the model mouse but also in human psoriasis. Treatment with STA-21 markedly inhibited the cytokine-dependent nuclear translocation of Stat3 in normal human keratinocytes in vitro. Keratinocyte proliferation was inhibited by STA-21 in a dose-dependent manner through downregulation of c-Myc and cyclin D1, whereas involucrin, transglutaminase 1, and keratin 10 levels were upregulated. Topical application of STA-21 abolished the generation of skin lesions in K5.Stat3C mice. Finally, we treated psoriasis patients with STA-21-containing ointment in a nonrandomized study. Psoriatic lesions in six of the eight patients showed improvement after topical STA-21 treatment for 2 weeks. Therefore, we conclude that targeting Stat3 may lead to a therapy for psoriasis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
STAT3Humanpsoriasis treatmentIMP  RGD 
Stat3Ratpsoriasis treatmentISOSTAT3 (Homo sapiens) RGD 
Stat3Mousepsoriasis treatmentISOSTAT3 (Homo sapiens) 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