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- W4285992275 abstract "Fibrosis is characterized by collagen deposition, fibro/myofibroblast accumulation, and extracellular matrix remodeling. Fibrosis can be seen in autoimmune diseases where it may be widespread and affect organs beyond the skin, with high morbidity and mortality, and no effective treatment. In cutaneous lupus, scar formation after discoid lesion eruption may evolve from enhanced fibrotic phenotypes. Our research has shown that epidermal-directed overexpression of murine Vgll3 causes severe lupus-like skin lesions suggestive of discoid lupus erythematosus (DLE). Given the apparent fibrotic nature of the skin lesions in transgenic (TG) Vgll3 mice, we wanted to determine if Vgll3 induces fibrosis. We analyzed male and female TG and wild-type (WT) mice aged 2-3 months. Fibrotic biomarkers of human DLE and scleroderma were analyzed. Epidermal Vgll3 overexpression resulted in development of not only cutaneous inflammation, but also severe fibrosis characterized by significant expression of fibrotic biomarkers found in human DLE and scleroderma lesions. Overall, lesional Vgll3 TG skin exhibited higher expression of Col1a1, Col1a2, Tgfb1 and Ctgf. ScRNA-seq of Vgll3 TG lesional skin vs. WT skin demonstrated that the increased expression of these collagen genes was localized to fibroblast (FB) and myofibroblast populations. Four FB subclusters were identified across all samples, with one detected almost exclusively in Vgll3 TG skin. This subcluster was distinguished by higher expression of Col1a1, Col1a2, Tgfb1, Ly6c1 and Eln. The presence of this unique FB subcluster in the skin of Vgll3 TG mice suggests that epidermal overexpression of Vgll3 impacts fibrosis development, and there may be a role for this unique FB subcluster in early fibrosis." @default.
- W4285992275 created "2022-07-21" @default.
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- W4285992275 date "2022-08-01" @default.
- W4285992275 modified "2023-10-18" @default.
- W4285992275 title "777 Overexpression of Vgll3 induces cutaneous fibrosis in a mouse model of lupus-like autoimmunity using single-cell RNA analyses" @default.
- W4285992275 doi "https://doi.org/10.1016/j.jid.2022.05.790" @default.
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