Ruiqi Tang, Hua Zha, Rongrong Liu, Jiawen Lv, Dan Cao, Lanjuan Li
{"title":"丁酸钠通过促进H4K8巴豆酰化来减缓肝纤维化。","authors":"Ruiqi Tang, Hua Zha, Rongrong Liu, Jiawen Lv, Dan Cao, Lanjuan Li","doi":"10.1007/s11010-025-05274-3","DOIUrl":null,"url":null,"abstract":"<p><p>Sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitor derived from dietary sources, demonstrates its potential in improving liver fibrosis in mice. This study explored NaB's impact on liver fibrosis through histone crotonylation. In vitro, NaB significantly inhibited the growth of TGF-β-stimulated LX2 hepatic stellate cells and reduced the expression of fibrotic markers ACTA2, the encoding gene of αSMA, and COL1A1 proportionally to the dosage. In vivo, NaB treatment of CCl<sub>4</sub>-induced ICR mice led to notable gains in liver function and a marked suppression in liver fibrosis. NaB inhibited Hdac2 and Hdac3 expression leading to increased H4K8 crotonylation, and modulated key fibrosis-related genes, providing a mechanistic basis for its therapeutic potential. Trichostatin A (TSA) exhibited similar effects to NaB, supporting the importance of HDAC inhibition in modulating these pathways. Overall, NaB's modulation of HDAC activity and histone crotonylation reveals a novel mechanism underlying its impact on liver fibrosis, highlighting its promise as a treatment for liver disease.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4467-4481"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sodium butyrate attenuates liver fibrogenesis via promoting H4K8 crotonylation.\",\"authors\":\"Ruiqi Tang, Hua Zha, Rongrong Liu, Jiawen Lv, Dan Cao, Lanjuan Li\",\"doi\":\"10.1007/s11010-025-05274-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitor derived from dietary sources, demonstrates its potential in improving liver fibrosis in mice. This study explored NaB's impact on liver fibrosis through histone crotonylation. In vitro, NaB significantly inhibited the growth of TGF-β-stimulated LX2 hepatic stellate cells and reduced the expression of fibrotic markers ACTA2, the encoding gene of αSMA, and COL1A1 proportionally to the dosage. In vivo, NaB treatment of CCl<sub>4</sub>-induced ICR mice led to notable gains in liver function and a marked suppression in liver fibrosis. NaB inhibited Hdac2 and Hdac3 expression leading to increased H4K8 crotonylation, and modulated key fibrosis-related genes, providing a mechanistic basis for its therapeutic potential. Trichostatin A (TSA) exhibited similar effects to NaB, supporting the importance of HDAC inhibition in modulating these pathways. Overall, NaB's modulation of HDAC activity and histone crotonylation reveals a novel mechanism underlying its impact on liver fibrosis, highlighting its promise as a treatment for liver disease.</p>\",\"PeriodicalId\":18724,\"journal\":{\"name\":\"Molecular and Cellular Biochemistry\",\"volume\":\" \",\"pages\":\"4467-4481\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s11010-025-05274-3\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05274-3","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/3 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
丁酸钠（NaB）是一种从饮食中提取的组蛋白去乙酰化酶（HDAC）抑制剂，证明了其改善小鼠肝纤维化的潜力。本研究通过组蛋白巴豆酰化探讨NaB对肝纤维化的影响。在体外，NaB显著抑制TGF-β刺激的LX2肝星状细胞的生长，并按剂量成比例降低纤维化标志物α - sma编码基因ACTA2和COL1A1的表达。在体内，NaB处理ccl4诱导的ICR小鼠导致肝功能显著改善，肝纤维化明显抑制。NaB抑制Hdac2和Hdac3的表达，导致H4K8巴豆酰化增加，并调节关键的纤维化相关基因，为其治疗潜力提供了机制基础。Trichostatin A （TSA）表现出与NaB相似的作用，支持HDAC抑制在调节这些途径中的重要性。总的来说，NaB对HDAC活性和组蛋白巴豆酰化的调节揭示了其影响肝纤维化的新机制，突出了其作为肝脏疾病治疗的前景。
Sodium butyrate attenuates liver fibrogenesis via promoting H4K8 crotonylation.
Sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitor derived from dietary sources, demonstrates its potential in improving liver fibrosis in mice. This study explored NaB's impact on liver fibrosis through histone crotonylation. In vitro, NaB significantly inhibited the growth of TGF-β-stimulated LX2 hepatic stellate cells and reduced the expression of fibrotic markers ACTA2, the encoding gene of αSMA, and COL1A1 proportionally to the dosage. In vivo, NaB treatment of CCl4-induced ICR mice led to notable gains in liver function and a marked suppression in liver fibrosis. NaB inhibited Hdac2 and Hdac3 expression leading to increased H4K8 crotonylation, and modulated key fibrosis-related genes, providing a mechanistic basis for its therapeutic potential. Trichostatin A (TSA) exhibited similar effects to NaB, supporting the importance of HDAC inhibition in modulating these pathways. Overall, NaB's modulation of HDAC activity and histone crotonylation reveals a novel mechanism underlying its impact on liver fibrosis, highlighting its promise as a treatment for liver disease.
期刊介绍：
Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell.
In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
