Wogonin induces hepatic stellate cell senescence by regulating the HDACs/p21<sup>Cip1</sup> signaling pathway

He Honglin; Liang Ailing; Lei Yao; Yu Jiamei; Yang Yunheng; Chen Zhiwei

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Wogonin induces hepatic stellate cell senescence by regulating the HDACs/p21^Cip1 signaling pathway

更新时间：2026-03-02

- Wogonin induces hepatic stellate cell senescence by regulating the HDACs/p21^Cip1 signaling pathway
- Journal of Chongqing Medical University Pages: 1-9(2026)
- 作者机构：
  
  1.重庆中医药学院中医学院，重庆 402760
  2.重庆医科大学中医药学院，中医药防治代谢性疾病重庆市重点实验室，重庆 400016
- 作者简介：
- 基金信息：
- DOI：
  CLC： R96
- Received：08 July 2025，
  
  Revised：2026-01-16，
  
  Accepted：19 January 2026，
  
  Published：02 March 2026
- 稿件说明：
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He Honglin,Liang Ailing,Lei Yao,et al.Wogonin induces hepatic stellate cell senescence by regulating the HDACs/p21^Cip1 signaling pathway[J].Journal of Chongqing Medical University,
DOI：

He Honglin,Liang Ailing,Lei Yao,et al.Wogonin induces hepatic stellate cell senescence by regulating the HDACs/p21^Cip1 signaling pathway[J].Journal of Chongqing Medical University, DOI：10.13406/j.cnki.cyxb..

摘要

目的

探讨汉黄芩素（wogonin，Wog）对肝星状细胞活化的影响，并研究其促进细胞衰老的潜在机制。

方法

使用大鼠肝星状细胞系（HSC-T6），进行不同浓度Wog（0、10、20、40 μmol/L）处理。采用转录组学、实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction，qPCR）和蛋白免疫印迹（Western blot）检测细胞活化及纤维化指标水平；采用衰老相关β-半乳糖苷酶（senescence-ass

ociated β-galactosidase，SA-β-gal）染色法分析细胞衰老状态；使用细胞计数试剂盒（Cell Counting Kit-8，CCK8）和5-乙炔基-2’-脱氧尿嘧啶（5-Ethynyl-2’-deoxyuridine，EdU）染色法检测HSC-T6细胞增殖情况；小干扰RNA（small interfering RNA，siRNA）技术用于明确p21

Cip1

基因在Wog诱导细胞衰老中的关键作用。

结果

基因集富集分析（gene set enrichment analysis，GSEA）显示，胶原蛋白等细胞外基质（extracellular matrix，ECM）相关基因集下调qPCR显示Wog显著抑制I型胶原α1链（collagen type I alpha 1 chain，COL1α1）、α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）和纤连蛋白（fibronectin，FN）的mRNA表达，Western blot进一步证明了这个结果Wog增加SA-β-gal阳性细胞比例，同时，qPCR结果显示Wog上调衰老标志物高迁移率族A1（high mobility group AT-hook 1，HMGA1）和白细胞介素6（interleukin 6，IL6）的表达，抑制周期相关蛋白Cyclin B1、Cyclin D1和周期蛋白依赖性激酶6（cyclin-dependent kinase 6，CDK6）的表达；Western blot进一步显示Wog下调HSC-T6细胞中组蛋白去乙酰化酶（histone deacetylase，HDAC）的表达，同时增加组蛋白H3赖氨酸14乙酰化（histone H3 lysine 14 acetylation，H3K14ac）水平。此外，Wog上调p21

Cip1

的表达，而p21

Cip1

敲低后可以减轻Wog诱导的肝星状细胞衰老现象。

结论

Wog可以作为HDAC抑制剂用于缓解肝纤维化，其机制是通过调控p21

Cip1

通路激活肝星状细胞衰老。

Abstract

Objective

To investigate the effect of wogonin（Wog） on hepatic stellate cell （HSC） activation and its potential mechanism of action in promoting cell senescence.

Methods

Rat hepatic stellate cells（HSC-T6） were treated with varying concentrations of Wog （0，10，20，40 μmol/L）. Transcriptomics，quantitative real-time PCR（qPCR），and Western blotting were used to measure the levels of cell activation and fibrosis markers；senescence-associated β-galactosidase（SA-β-gal） staining was used to assess the state of cell senescence； CCK8 assay and 5-ethynyl-2′-deoxyuridine staining were used to measure the proliferation of HSC-T6 cells；the small interfering RNA technique was used to clarify the key role of the p21

Cip1

gene in Wog-induced cell senescence.

Results

The Gene Set Enrichment Analysis showed downregulation of extracellular matrix-related gene sets，including collagen. The results of qPCR s

howed that Wog significantly inhibited the mRNA expression levels of collagen type I alpha 1 chain，α-smooth muscle actin，and fibronectin，which was further confirmed by Western blotting. Wog increased the percentage of SA-β-gal-positive HSCs，and meanwhile，the results of qPCR showed that Wog upregulated the expression levels of the senescence markers high-mobility group AT-hook 1 and interleukin-6 and downregulated the expression levels of Cyclin B1，Cyclin D1，and cyclin-dependent kinase 6. The results of Western blotting further showed that Wog could reduce the expression of histone deacetylase（HDAC） and increase the level of histone H3 lysine 14 acetylation in HSC-T6 cells. In addition，Wog upregulated the expression of p21

Cip1

，and knockdown of p21

Cip1

could alleviate HSC senescence induced by Wog.

Conclusion

Wog can be used as an HDAC inhibitor to alleviate hepatic fibrosis by activating HSC senescence through the p21

Cip1

signaling pathway.

关键词

Keywords

references

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⁰

Wogonin induces hepatic stellate cell senescence by regulating the HDACs/p21Cip1 signaling pathway

DOI：

摘要

Abstract

关键词

Keywords

references

Wogonin induces hepatic stellate cell senescence by regulating the HDACs/p21^Cip1 signaling pathway