joi, 12 martie 2009

ce spun japonezii despre psoriazis

Impact of Stat3 activation upon skin biology: a dichotomy of its role
between homeostasis and diseases.
Sano S, Chan KS, DiGiovanni J.

Department of Dermatology, Kochi Medical School, Kochi University,
Okocho, Nankoku, Kochi 783-8505, Japan.

Signal transducer and activator of transcription 3 (Stat3) is a latent
cytoplasmic protein that conveys signals to the nucleus upon
stimulation with IL-6, EGF, and many other cytokines/growth factors,
leading to transcriptional activation of the downstream genes. It has
been well defined that Stat3 plays critical roles in biological
activities including cell proliferation, migration, survival, and
oncogenesis. The in vivo role for Stat3 in the skin was elucidated
using keratinocyte-specific Stat3 gene knockout mice, referred to as
Stat3-disrutped mice. It was shown that Stat3 activation contributed
to skin wound healing, keratinocyte migration, hair follicle growth,
and resistance to UV irradiation-induced apoptosis. Furthermore, in
the two-stage chemical carcinogenesis protocol, Stat3-disrupted mice
did not develop any skin tumors. In contrast, transgenic mice with a
constitutive active form of Stat3 (K5.Stat3C mice) developed squamous
cell carcinoma (SCC) with a shorter latency and in much greater number
compared to control mice. These results suggested a role for Stat3 not
only in early stages of skin carcinogenesis but also in driving
malignant progression in vivo. Moreover, Stat3 was consistently
activated in epidermal keratinocytes in human psoriatic lesions, which
has been assumed to recapitulate a condition of persistent wound
healing reaction. Accordingly, K5.Stat3C mice were found to be
psoriasis-prone. Finally, it was demonstrated that an inhibition of
Stat3 activation ameliorated these pathological conditions, i.e., skin
carcinogenesis and psoriasis. Here we will review the dichotomous
roles for Stat3 in maintaining skin homeostasis and in the development
of skin diseases such as psoriasis and skin cancer.

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