Scholarlink

Background <p>Smoking, a persistent and widespread unhealthy habit, poses significant toxicity to the liver. However, research on how nicotine metabolite cotinine specifically relates to liver fibrosis remains incomplete.</p> Objectives <p>This study sought to uncover the molecular mechanism linking cotinine and liver fibrosis.</p> Methods <p>Utilizing data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional analysis was conducted to compare cotinine serum levels between individuals with and without liver fibrosis. In addition, network pharmacology, molecular docking, and in vitro experiments were employed to comprehensively explore the molecular mechanism and potential key targets of cotinine-induced liver fibrosis.</p> Results <p>NHANES data analysis revealed significantly higher cotinine levels in patients with liver fibrosis. Network pharmacology analysis identified 60 common metabolite disease targets between cotinine and liver fibrosis, primarily involved in metabolic pathways and P450 metabolic processes. Key targets included HSP90AA1, CYP19A1, CYP17A1, CYP11B2, AR, and CDK2. In vitro experiments confirmed these findings, showing that cotinine promotes the mRNA expression of liver fibrosis-related genes and HSP90AA1, P450 metabolism-related genes. This suggests that cotinine may facilitate liver fibrosis through the HSP90AA1/P450s pathway.</p> Conclusions <p>This study indicates that serum cotinine levels may serve as a crucial indicator for liver fibrosis monitoring. Furthermore, cotinine may induce liver fibrosis via the HSP90AA1/P450s pathway, providing a new perspective and potential therapeutic target for predicting, evaluating, and alleviating smoking-related liver fibrosis.</p> Graphical abstract <p>The diagram illustrates the potential mechanism by which cotinine is involved in liver fibrosis. <b>A</b> Analysis of serum levels of cotinine in smoking and non-smoking patients based on NHANES database. <b>B</b> Screening of pathogenic genes related to liver fibrosis. C Network pharmacological analysis. <b>D</b> Molecular docking and in vitro experimental verification</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

HSP90AA1/P450s as a new target of nicotine metabolite cotinine induced liver fibrosis: a comprehensive approach

  • 期刊论文

  • 发表日期：

    2025年5月22日

查看全文
  • Yongfei He,
  • Junming Xu,
  • Shengjie Hong,
  • Qiang Tao

摘要

Background

Smoking, a persistent and widespread unhealthy habit, poses significant toxicity to the liver. However, research on how nicotine metabolite cotinine specifically relates to liver fibrosis remains incomplete.

Objectives

This study sought to uncover the molecular mechanism linking cotinine and liver fibrosis.

Methods

Utilizing data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional analysis was conducted to compare cotinine serum levels between individuals with and without liver fibrosis. In addition, network pharmacology, molecular docking, and in vitro experiments were employed to comprehensively explore the molecular mechanism and potential key targets of cotinine-induced liver fibrosis.

Results

NHANES data analysis revealed significantly higher cotinine levels in patients with liver fibrosis. Network pharmacology analysis identified 60 common metabolite disease targets between cotinine and liver fibrosis, primarily involved in metabolic pathways and P450 metabolic processes. Key targets included HSP90AA1, CYP19A1, CYP17A1, CYP11B2, AR, and CDK2. In vitro experiments confirmed these findings, showing that cotinine promotes the mRNA expression of liver fibrosis-related genes and HSP90AA1, P450 metabolism-related genes. This suggests that cotinine may facilitate liver fibrosis through the HSP90AA1/P450s pathway.

Conclusions

This study indicates that serum cotinine levels may serve as a crucial indicator for liver fibrosis monitoring. Furthermore, cotinine may induce liver fibrosis via the HSP90AA1/P450s pathway, providing a new perspective and potential therapeutic target for predicting, evaluating, and alleviating smoking-related liver fibrosis.

Graphical abstract

The diagram illustrates the potential mechanism by which cotinine is involved in liver fibrosis. A Analysis of serum levels of cotinine in smoking and non-smoking patients based on NHANES database. B Screening of pathogenic genes related to liver fibrosis. C Network pharmacological analysis. D Molecular docking and in vitro experimental verification