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<p>Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by progressive skin and organ fibrosis. Although interferon signaling is dysregulated in SSc, the role of interferon-induced proteins like IFIT3 in the skin fibrosis of SSC remains unclear. Here, we demonstrate that IFIT3 expression is significantly elevated (<i>p</i> &lt; 0.01) in SSc fibroblasts and promotes fibrosis via SOCS1-dependent activation of the EGFR/VEGF axis. Silencing IFIT3 upregulated SOCS1 (<i>p</i> &lt; 0.05), suppressed EGFR/VEGF (<i>p</i> &lt; 0.01), and inhibited fibroblast proliferation/migration (<i>p</i> &lt; 0.01). In a bleomycin-induced SSc model, IFIT3 knockdown ameliorated skin/lung collagen deposition and fibrosis (<i>p</i> &lt; 0.05). Our findings reveal a novel mechanism whereby IFIT3 regulates EGFR and VEGF through down-regulating SOCS1 in SSc fibrosis, identifying IFIT3 as a novel therapeutic target for SSc.</p>

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Silencing IFIT3 suppresses the EGFR/VEGF pathway and modulates SOCS1 to attenuate skin fibrosis in systemic sclerosis

  • 期刊论文

  • 发表日期：

    2025年6月14日

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  • Xiangyang Huang,
  • Yi Liu,
  • Hangling Fu,
  • Xia Rong,
  • Yiheng Zhao

摘要

Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by progressive skin and organ fibrosis. Although interferon signaling is dysregulated in SSc, the role of interferon-induced proteins like IFIT3 in the skin fibrosis of SSC remains unclear. Here, we demonstrate that IFIT3 expression is significantly elevated (p < 0.01) in SSc fibroblasts and promotes fibrosis via SOCS1-dependent activation of the EGFR/VEGF axis. Silencing IFIT3 upregulated SOCS1 (p < 0.05), suppressed EGFR/VEGF (p < 0.01), and inhibited fibroblast proliferation/migration (p < 0.01). In a bleomycin-induced SSc model, IFIT3 knockdown ameliorated skin/lung collagen deposition and fibrosis (p < 0.05). Our findings reveal a novel mechanism whereby IFIT3 regulates EGFR and VEGF through down-regulating SOCS1 in SSc fibrosis, identifying IFIT3 as a novel therapeutic target for SSc.