Latent TGFbeta1 overexpression in keratinocytes results in a severe psoriasis-like skin disorder.
Transforming growth factor beta1 (TGFbeta1), 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 TGFbeta1 in the epidermis using a keratin 5 promoter (K5.TGFbeta1(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.TGFbeta1(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 TGFbeta1 overexpression in the skin may synergize with or induce molecules required for the development of Th1 inflammatory skin disorders.
Li
Allen G
AG
Department of Otolaryngology, Oregon Health & Science University, Portland, OR, USA.
Wang
Donna
D
Feng
Xin-Hua
XH
Wang
Xiao-Jing
XJ
D000818:Animals; D001485:Basement Membrane / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D012867:Skin / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D016207:Cytokines; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1