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- Title
Transforming growth factor- β1 mediates psoriasis-like lesions via a Smad3-dependent mechanism in mice.
- Authors
Zhang, Yun; Meng, Xiao‐Ming; Huang, Xiao‐Ru; Wang, Xiao‐Jing; Yang, Liu; Lan, Hui Yao
- Abstract
Transforming growth factor ( TGF)- β1 signals through downstream Smad-dependent and -independent pathways to exert its biological actions. It has been reported that overexpression of TGF- β1 results in the development of psoriasis-like lesions in a mouse model of K5. TGF- β WT transgenic mice. However, the signalling mechanisms by which TGF- β1 mediates the development of psoriasis-like lesions remain unknown. The aim of the present study was to investigate the hypothesis that TGF- β1 mediates the development of psoriasis-like lesions via a Smad3-dependent mechanism. This was tested in a mouse model of K5. TGF- β WT transgenic mice by blocking TGF- β signalling with a specific Smad3 inhibitor. Topical treatment with a Smad3 inhibitor markedly blocked TGF- β/Smad3 signalling and progressive psoriasis-like lesions in K5. TGF- β WT transgenic mice, as evidenced by decreased skin severity scores, double skin fold thickness ( DSFT) scores, infiltration of CD3+ T cells and F4/80+ macrophages and the degree of fibrosis in the dermis. This was associated with a marked reduction in TGF- β1, interleukin ( IL)-6, IL-23 and IL-17A both locally in skin plaque lesions and systemically in the plasma, resulting in inhibition of both the T helper (Th) 17 cell transcription factor ROR γt and accumulation of CD4+ IL-17A+ cells within the skin plaque lesions. In conclusion, TGF- β1 mediates the development of psoriasis-like lesions via a Smad3-dependent, Th17-mediated mechanism. Targeting TGF- β/Smad3 signalling with a Smad3 inhibitor may represent a novel and effective therapy for psoriasis.
- Subjects
ENDOTHELIAL growth factors; BIOCHEMICAL mechanism of action; TRANSGENIC animals; CELL-mediated cytotoxicity; LABORATORY mice
- Publication
Clinical & Experimental Pharmacology & Physiology, 2014, Vol 41, Issue 11, p921
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12294