{"title":"Exploring the toxicological network of bleomycin-induced pulmonary fibrosis: The role of long non-coding RNAs","authors":"Bingxin Li, Hongbin Shi, Yun Ma, Ruining Zhao, Haijun Zhang","doi":"10.1016/j.fct.2025.115723","DOIUrl":null,"url":null,"abstract":"<div><div>Bleomycin (BLM) is an effective anticancer agent; however, its clinical use is limited by its tendency to induce pulmonary fibrosis (PF), a complication whose molecular mechanisms remain unclear. In this study, we established a BLM-induced C57BL/6 mouse model of PF and applied total RNA-seq in combination with network toxicology approaches to investigate the role of long noncoding RNAs (lncRNAs) in this process. The lncRNA Xist was identified as a hub node in the network, regulating the expression of its target Mmp25 via interaction with miR-34a-5p and miR-449c-5p. Further Gene Ontology and KEGG pathway analyses suggested that BLM may promote PF by modulating the TGF-β signaling pathway. Importantly, siRNA-mediated knockdown of Xist in vitro significantly attenuated BLM-induced cellular injury and suppressed TGF-β pathway activation, confirming its functional involvement. These findings provide novel insights into the molecular basis of BLM-induced PF from an lncRNA perspective and highlight Xist as a potential therapeutic target for mitigating the drug's pulmonary toxicity.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"206 ","pages":"Article 115723"},"PeriodicalIF":3.5000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Food and Chemical Toxicology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0278691525004910","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Bleomycin (BLM) is an effective anticancer agent; however, its clinical use is limited by its tendency to induce pulmonary fibrosis (PF), a complication whose molecular mechanisms remain unclear. In this study, we established a BLM-induced C57BL/6 mouse model of PF and applied total RNA-seq in combination with network toxicology approaches to investigate the role of long noncoding RNAs (lncRNAs) in this process. The lncRNA Xist was identified as a hub node in the network, regulating the expression of its target Mmp25 via interaction with miR-34a-5p and miR-449c-5p. Further Gene Ontology and KEGG pathway analyses suggested that BLM may promote PF by modulating the TGF-β signaling pathway. Importantly, siRNA-mediated knockdown of Xist in vitro significantly attenuated BLM-induced cellular injury and suppressed TGF-β pathway activation, confirming its functional involvement. These findings provide novel insights into the molecular basis of BLM-induced PF from an lncRNA perspective and highlight Xist as a potential therapeutic target for mitigating the drug's pulmonary toxicity.
期刊介绍:
Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs.
The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following:
-Adverse physiological/biochemical, or pathological changes induced by specific defined substances
-New techniques for assessing potential toxicity, including molecular biology
-Mechanisms underlying toxic phenomena
-Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability.
Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.