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- W4313340069 abstract "Systemic sclerosis (SSc) is a chronic, heterogeneous disease of connective tissue characterized by organ fibrosis together with vascular injury and autoimmunity. TGF-β plays a central role in generating fibrosis, including SSc. Periostin is a matricellular protein playing a key role in the generation of fibrosis by amplifying the TGF-β signals. SOX11 is a transcription factor playing several important roles in organ development in embryos. We have previously shown that SOX11 induces periostin expression. However, the roles of the interactions among the TGF-β signals, periostin, and SOX11 remain unknown in the pathogenesis of SSc. In this study, we found that most clones of dermal fibroblasts derived from patients with SSc showed constitutive, high expression of SOX11, which is significantly induced by TGF-β1. SOX11 forms a positive loop with periostin to activate the TGF-β signals in SSc dermal fibroblasts. Genetic deletion of Sox11 in Postn-expressing fibroblasts impairs dermal fibrosis by bleomycin. Moreover, using the DNA microarray method, we identified several fibrotic factors dependent on the TGF-β/SOX11/periostin pathway in SSc dermal fibroblasts. Our findings, taken together, show that a positive loop formed by SOX11 and periostin in fibroblasts upregulates the TGF-β signals, leading to skin fibrosis." @default.
- W4313340069 created "2023-01-06" @default.
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- W4313340069 date "2023-06-01" @default.
- W4313340069 modified "2023-09-30" @default.
- W4313340069 title "A Positive Loop Formed by SOX11 and Periostin Upregulates TGF-β Signals Leading to Skin Fibrosis" @default.
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- W4313340069 doi "https://doi.org/10.1016/j.jid.2022.12.008" @default.
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