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Latent TGFβ1 overexpression in keratinocytes results in a severe psoriasis‐like skin disorder
Author(s) -
Li Allen G,
Wang Donna,
Feng XinHua,
Wang XiaoJing
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600183
Subject(s) - biology , psoriasis , keratinocyte , transforming growth factor , dermatology , cancer research , immunology , genetics , microbiology and biotechnology , cell culture , medicine
Transforming growth factor β1 (TGFβ1), a potent keratinocyte growth inhibitor, has been shown to be overexpressed in keratinocytes in certain inflammatory skin diseases and has been thought to counteract the effects of other growth factors at the site of inflammation. Surprisingly, our transgenic mice expressing wild‐type TGFβ1 in the epidermis using a keratin 5 promoter (K5.TGFβ1 wt ) developed inflammatory skin lesions, with gross appearance of psoriasis‐like plaques, generalized scaly erythema, and Koebner's phenomenon. These lesions were characterized by epidermal hyperproliferation, massive infiltration of neutrophils, T lymphocytes, and macrophages to the epidermis and superficial dermis, subcorneal microabscesses, basement membrane degradation, and angiogenesis. K5.TGFβ1 wt skin exhibited multiple molecular changes that typically occur in human Th1 inflammatory skin disorders, such as psoriasis. Further analyses revealed enhanced Smad signaling in transgenic epidermis and dermis. Our study suggests that certain pathological condition‐induced TGFβ1 overexpression in the skin may synergize with or induce molecules required for the development of Th1 inflammatory skin disorders.