Scholarlink

<p>Drug-induced liver injury (DILI) is a leading cause of acute liver failure, posing a significant public health burden. Emerging evidence underscores the gut microbiota as a critical environmental factor that profoundly influences liver function and DILI progression, yet the underlying mechanisms remain poorly understood. Here, we identify hepatic long non-coding RNA <i>SNHG9</i> as a key mediator linking the gut microbiota to acetaminophen (APAP)-induced liver injury. Upregulation of hepatic <i>SNHG9</i> protects against hepatotoxicity by activating MAS, a G protein-coupled receptor that facilitates the clearance of cellular damage via enhanced autophagy. Mechanistically, <i>SNHG9</i> binds to insulin-like growth factor 2 mRNA-binding protein 2 (IMP2), enhancing its interaction with <i>MYC</i> mRNA and suppressing <i>MYC</i> translation. Since MYC acts as a transcriptional repressor of the <i>MAS1</i> gene, this suppression leads to upregulated MAS expression. Notably, hepatic <i>SNHG9</i> expression is modulated by the gut microbiota, particularly through the metabolite 2-hydroxy 2-methylbutyric acid (HMB). Supplementation with HMB or HMB-producing microbes robustly induces hepatic <i>SNHG9</i> expression and attenuates APAP-induced liver injury. Our findings unveil a previously unrecognized gut-liver axis and provide mechanistic insight into how gut microbiota regulate hepatic stress responses, suggesting potential avenues for modulating this pathway in drug-induced liver injury.</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

Hepatic SNHG9 links gut microbiota to liver protection in drug-induced liver injury

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月20日

查看全文
  • Wu Bao,
  • Bingqing Hang,
  • Danyi Zeng,
  • Jiajie Mao,
  • Li-Bin Pan,
  • Lichao Wang,
  • Guangyi Xu,
  • Meng Wang,
  • Kailin Liu,
  • Xianjiong Chen,
  • Xinyi Zhu,
  • Guifang Li,
  • Daqian Xu,
  • Gaopeng Li,
  • Yuan Ding,
  • Qiming Liang,
  • Xiaobing Dou,
  • Wangyun Xu,
  • Jiaxin Chen,
  • Jinshui Pan,
  • Yanhui Lu,
  • Yuhao Wang

摘要

Drug-induced liver injury (DILI) is a leading cause of acute liver failure, posing a significant public health burden. Emerging evidence underscores the gut microbiota as a critical environmental factor that profoundly influences liver function and DILI progression, yet the underlying mechanisms remain poorly understood. Here, we identify hepatic long non-coding RNA SNHG9 as a key mediator linking the gut microbiota to acetaminophen (APAP)-induced liver injury. Upregulation of hepatic SNHG9 protects against hepatotoxicity by activating MAS, a G protein-coupled receptor that facilitates the clearance of cellular damage via enhanced autophagy. Mechanistically, SNHG9 binds to insulin-like growth factor 2 mRNA-binding protein 2 (IMP2), enhancing its interaction with MYC mRNA and suppressing MYC translation. Since MYC acts as a transcriptional repressor of the MAS1 gene, this suppression leads to upregulated MAS expression. Notably, hepatic SNHG9 expression is modulated by the gut microbiota, particularly through the metabolite 2-hydroxy 2-methylbutyric acid (HMB). Supplementation with HMB or HMB-producing microbes robustly induces hepatic SNHG9 expression and attenuates APAP-induced liver injury. Our findings unveil a previously unrecognized gut-liver axis and provide mechanistic insight into how gut microbiota regulate hepatic stress responses, suggesting potential avenues for modulating this pathway in drug-induced liver injury.