中国临床药理学杂志

SESN2激活ULK1介导JNK信号通路在肝星状细胞活化中的调节机制

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汤洁 ¹^,² , 马天奇 ¹ , 姜正伟 ¹^,² , 景源伟 ¹ , 孙路翔 ¹ , 程宏 ¹

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(23): 3358-3365

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (23) : 3358 -3365

SESN2激活ULK1介导JNK信号通路在肝星状细胞活化中的调节机制

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汤洁¹^,², 马天奇¹, 姜正伟¹^,², 景源伟¹, 孙路翔¹, 程宏¹

作者信息

^1.扬州大学医学部，江苏扬州 225001

^2，淮安市第四人民医院肝病科，江苏淮安 223002

通讯作者:

程宏，副教授 MP: 13773528387 E-mail: hcheng@yzu.edu.cn

作者简介:

汤洁（1988-），女，在读硕士，主要从事肝炎、肝硬化、肝硬化失代偿期并发症、肝癌的诊治研究

SESN2 activation of ULK1 mediates the regulatory mechanism of JNK signaling pathway in hepatic stellate cell activation

Jie TANG¹^,², Tian-qi MA¹, Zheng-wei JIANG¹^,², Yuan-wei JING¹, Lu-xiang SUN¹, Hong CHENG¹

Affiliations

^1.Faculty of Medicine, Yangzhou University, Yangzhou 225001, Jiangsu Province, China

^2.Department of Hepatology, The Fourth People’s Hospital of Huai’an, Huai’an 223002, Jiangsu Province, China

出版时间: 2025-12-17 doi: 10.13699/j.cnki.1001-6821.2025.23.009

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摘要

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目的

探讨应激诱导蛋白2（SESN2）通过unc-51样激酶1（ULK1）对JS-1细胞活化的作用及其机制。

方法

将JS-1细胞分为对照组（正常培养）、si-NC组（转染si-NC）、si-SESN2组（转染si-SESN2）、模型组（含5 μg·L^-1转化生长因子-β1的培养基培养24 h）、模型+oe-SESN2组（模型组基础上转染oe-SESN2）、模型+si-SESN2组（模型组基础上转染si-SESN2）、模型+si-SESN2+oe-ULK1组（模型组基础上共转染si-SESN2和oe-ULK1）。免疫荧光检测F-肌动蛋白（F-actin）水平；实时定量反转录聚合酶链式反应检测ULK1 mRNA水平；蛋白免疫印迹检测SESN2、微管相关蛋白轻链3 Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ）、结缔组织生长因子（CTGF）、I型胶原α1（Col1a1）、磷酸化-应激活化蛋白激酶（p-JNK）、应激活化蛋白激酶（JNK）、c-Jun、激活转录因子2（ATF2）相对表达水平；细胞计数试剂盒-8检测细胞增殖率；Transwell检测细胞侵袭能力。

结果

对照组、模型组、模型+oe-SESN2组和模型+si-SESN2组SESN2蛋白的相对表达水平分别为1.00±0.19、2.57±0.49、3.61±0.68和1.66±0.31，F-actin相对荧光强度分别为1.00±0.18、4.57±0.92、6.33±1.19和2.81±0.57，ULK1 mRNA的相对表达水平分别为1.00±0.15、2.67±0.48、3.52±0.66和1.95±0.37。对照组、模型组、模型+oe-SESN2组、模型+si-SESN2组和模型+si-SESN2+oe-ULK1组LC3Ⅱ/Ⅰ蛋白的相对表达水平分别为1.00±0.20、2.79±0.53、3.57±0.68、1.88±0.35和2.51±0.48，细胞增殖率分别为（100.00±2.23）%、（141.31±4.17）%、（156.52±8.84）%、（109.49±7.35）%和（127.08±8.16）%，细胞侵袭个数分别为66.04±11.45、137.84±21.73、215.19±35.28、75.46±13.51和124.27±19.50，CTGF蛋白的相对表达水平分别为1.00±0.17、2.65±0.51、3.77±0.72、1.51±0.29和2.53±0.51，Col1a1蛋白的相对表达水平分别为1.00±0.15、2.93±0.57、3.88±0.75、1.61±0.31和2.72±0.52，JNK蛋白相对磷酸化水平分别为1.00±0.16、2.21±0.42、3.08±0.59、1.46±0.29和2.04±0.37。模型组上述指标与对照组比较，模型+oe-SESN2组或模型+si-SESN2组上述指标与模型组比较，模型+si-SESN2+oe-ULK1组上述指标与模型+si-SESN2组比较，在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001）。

结论

SESN2通过激活ULK1，促进JS-1细胞活化，促进细胞增殖和侵袭，调控细胞稳态，可能是通过激活JNK信号通路实现的。

关键词

应激诱导蛋白2 / unc-51样激酶1 / 肝星状细胞 / 应激活化蛋白激酶信号通路 / 细胞增殖

Abstract

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Objective

To investigate the effect of sestrin 2 (SESN2) on JS-1 cell activation through unc-51-like kinase 1 (ULK1) and its mechanism.

Methods

The JS-1 cells were divided into seven groups: the control group (cultured under normal conditions), si-NC group (transfected with si-NC), the si-SESN2 group (transfected with si-SESN2), model group (cultured in medium containing 5 μg·L^-1 transforming growth factor-β1 for 24 h), model + oe-SESN2 group (transfected with oe-SESN2 on the basis of the model group), model + si-SESN2 group (transfected with si-SESN2 on the basis of the model group), and model+si-SESN2 + oe-ULK1 group (co-transfected with si-SESN2 and oe-ULK1 on the basis of the model group). The levels of fibrous actin (F-actin) was detected by immunofluorescence. Quantitative real time polymerase chain reaction was used to detect the ULK1 mRNA level. The relevtive expression levels of SESN2, light chain 3 Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ), connective tissue growth factor (CTGF), collagen type I α1 (Col1a1), phospho-c-Jun N-terminal kinase (p-JNK), c-Jun N-terminal kinase (JNK), c-Jun and activating transcription factor 2 (ATF2) were detected by Western Blot. Cell proliferation rate was detected by cell counting kit-8. Transwell assesses the ability of cells to invade.

Results

The relative expression levels of SESN2 protein in the control group, model group, model+oe-SESN2 group, and model+si-SESN2 group were 1.00±0.19, 2.57±0.49, 3.61±0.68, and 1.66±0.31, respectively; the relative fluorescence intensity of F-actin was 1.00±0.18, 4.57±0.92, 6.33±1.19, and 2.81±0.57, respectively; the relative expression levels of ULK1 mRNA were 1.00±0.15, 2.67±0.48, 3.52±0.66, and 1.95±0.37, respectively. The relative expression levels of LC3Ⅱ/Ⅰ protein in the control group, model group, model+oe-SESN2 group, model+si-SESN2 group, and model+si-SESN2+oe-ULK1 group were 1.00±0.20, 2.79±0.53, 3.57±0.68, 1.88±0.35, and 2.51±0.48, respectively; the cell proliferation rates were (100.00±2.23)%, (141.31±4.17)%, (156.52±8.84)%, (109.49±7.35)%, and (127.08±8.16)%, respectively; the number of cell invasions was 66.04±11.45, 137.84±21.73, 215.19±35.28, 75.46±13.51, and 124.27±19.50, respectively; the relative expression levels of CTGF protein were 1.00±0.17, 2.65±0.51, 3.77±0.72, 1.51±0.29, and 2.53±0.51, respectively; the relative expression levels of Col1a1 protein were 1.00±0.15, 2.93±0.57, 3.88±0.75, 1.61±0.31, and 2.72±0.52, respectively; the relative phosphorylation levels of JNK protein were 1.00±0.16, 2.21±0.42, 3.08±0.59, 1.46±0.29, and 2.04±0.37, respectively. Compared with the control group, the above indicators of the model group showed statistically significant differences; compared with the model group, the above indicators of the model+oe-SESN2 group or model+si-SESN2 group showed statistically significant differences; compared with the model+si-SESN2 group, the above indicators of the model+si-SESN2+oe-ULK1 group all showed statistically significant differences (P<0.05, P<0.01, P<0.001).

Conclusion

SESN2 activates ULK1, promotes JS-1 cell activation, promotes cell proliferation and invasion, and regulates cell homeostasis, possibly through the activation of JNK signaling pathway.

Key words

sestrin 2 / unc-51-like kinase 1 / hepatic stellate cells / c-Jun N-terminal kinase signaling pathway / cell proliferation

引用本文

汤洁, 马天奇, 姜正伟, 景源伟, 孙路翔, 程宏. SESN2激活ULK1介导JNK信号通路在肝星状细胞活化中的调节机制. 中国临床药理学杂志, 2025 , 41 (23) : 3358 -3365 . DOI: 10.13699/j.cnki.1001-6821.2025.23.009

Jie TANG, Tian-qi MA, Zheng-wei JIANG, Yuan-wei JING, Lu-xiang SUN, Hong CHENG. SESN2 activation of ULK1 mediates the regulatory mechanism of JNK signaling pathway in hepatic stellate cell activation[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (23) : 3358 -3365 . DOI: 10.13699/j.cnki.1001-6821.2025.23.009

基金

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2024年度淮安市卫生健康科研基金资助项目(HAWJZ2024003)

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2025年第41卷第23期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.23.009

接收时间：2025-08-29
首发时间：2026-08-05
出版时间：2025-12-17

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收稿日期：2025-08-29

基金

2024年度淮安市卫生健康科研基金资助项目(HAWJZ2024003)

作者信息

^1.扬州大学医学部，江苏扬州 225001

^2，淮安市第四人民医院肝病科，江苏淮安 223002

通讯作者:

程宏，副教授 MP: 13773528387 E-mail: hcheng@yzu.edu.cn

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.23.009

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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