Scholarlink

<p>Hepatic fibrosis progression involves complex multicellular crosstalk, highlighting the critical need to identify key therapeutic targets. In this study, we identify insulin-like growth factor binding protein 6 (IGFBP6) as a marker specifically enriched in hepatic stellate cells (HSCs) and upregulated in viral hepatitis-associated fibrosis. Using thioacetamide (TAA)-induced mouse models and transforming growth factor-β (TGF-β)-stimulated cell models, we demonstrate the pro-fibrotic role of IGFBP6. Through network pharmacology screening, pantothenic acid (PA) is identified as a potent compound targeting IGFBP6. PA administration significantly reduces collagen deposition, attenuates HSCs’ activation, and decreases hepatic fibrosis-related markers. Notably, PA maintains efficacy in mouse models with established fibrosis. Mechanistically, PA directly interacts with IGFBP6, inducing ubiquitin-dependent degradation and inhibiting TGF-β/SMADs signaling. This study identifies IGFBP6 as a driver of hepatic fibrosis and validates PA as a potent therapeutic agent. Therefore, targeting IGFBP6 with PA offers a potential clinical treatment strategy for hepatic fibrosis.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pantothenic acid ameliorates hepatic fibrosis by targeting IGFBP6 to regulate the TGF-β/SMADs pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月29日

查看全文
  • Zhengxin Jin,
  • Zhengsen Jin,
  • Zeyu Liu,
  • Yongcheng Yin,
  • Yuchen Zhang,
  • Ying Zhang,
  • Jianning Kang,
  • Yuepeng Fang,
  • Wei Jiang,
  • Bin Ning

摘要

Hepatic fibrosis progression involves complex multicellular crosstalk, highlighting the critical need to identify key therapeutic targets. In this study, we identify insulin-like growth factor binding protein 6 (IGFBP6) as a marker specifically enriched in hepatic stellate cells (HSCs) and upregulated in viral hepatitis-associated fibrosis. Using thioacetamide (TAA)-induced mouse models and transforming growth factor-β (TGF-β)-stimulated cell models, we demonstrate the pro-fibrotic role of IGFBP6. Through network pharmacology screening, pantothenic acid (PA) is identified as a potent compound targeting IGFBP6. PA administration significantly reduces collagen deposition, attenuates HSCs’ activation, and decreases hepatic fibrosis-related markers. Notably, PA maintains efficacy in mouse models with established fibrosis. Mechanistically, PA directly interacts with IGFBP6, inducing ubiquitin-dependent degradation and inhibiting TGF-β/SMADs signaling. This study identifies IGFBP6 as a driver of hepatic fibrosis and validates PA as a potent therapeutic agent. Therefore, targeting IGFBP6 with PA offers a potential clinical treatment strategy for hepatic fibrosis.