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Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding rna h19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

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Journal of Integrative Medicine 2024年第2期22卷 188-198页

作者： Meng Li Yang Zhou hui Zhu Lie-ming Xu Jian Ping Institute of Liver Diseases Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Preventive Treatment Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437 China Department of Gastroenterology Suzhou Traditional Chinese Medicine HospitalSuzhou 215000Jiangsu ProvinceChina Shanghai Key Laboratory of Traditional Chinese Medicine Shanghai 201203China Key Laboratory of Liver and Kidney Diseases(Ministry of Education) Shanghai 201203China

Objective:This study explores the mechanism of action of Danhongqing formula(DhQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver ***:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver *** was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related ***-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DhQ on long non-coding rna h19(h19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-*** addition,cholangiocytes and hepatic stellate cells(hSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and h19 *** overexpressing h19 were constructed,and a conditioned medium containing h19 was collected to measure its effects on STAT3 protein expression and cell *** intervention effect of DhQ on these processes was also *** overexpressing h19 were constructed to measure the impact of h19 on cell activation and assess the intervention effect of ***:DhQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited h19expression,STAT3 expression and STAT3 *** formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of h19,inhibited the activation of hSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in *** overexpression of h19 in a human hSC line confirmed that h19 promoted STAT3 phosphorylation and hSC activation,and DhQ was able to successfully inhibit these ***:DhQ effectively alleviated spontaneous cholestatic liver fibrosis in Md

关键词： Liver cirrhosis biliary long non-coding rna h19 Danhongqing formula Cholangiocyte hepatic stellate cells STAT3 transcription factor

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Effects of OGG1 methylation regulated byh19/SAhh/DNMT1 on the oxidative DNA damage and cell cycle arrest related to PAhs exposure

Effects of OGG1 methylation regulated byH19/SAHH/DNMT1 on th...

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中国毒理学会第九次全国毒理学大会

作者： LI Xue-jing FU Ye PAN Bao-long NIUYing-ying ZhANG Bin ZhAO Xinyu NIEJi-sheng WANG Rui-sheng YANG Jin Department of Occupational health School of Public Health Shanxi Medical University General hospital of Taiyuan Iron ＆ Steel （Group） Co. Ltd.

OBJECTIVE To investigate the effects of OGG1 methylation regulated by h19/SAhh/DNMT1 on the oxidative DNA damage and cell cycle arrest related to PAhs exposure. METhODS We used high performance liquid chromatography mass spectrometry（hPLC-MS） equipped to detect urine biomarkers of PAhs exposure, including 2-hydroxynaphthalene（2-NAP）, 2-hydroxyfluorene（2-FLU）, 9-hydroxyphenanthrene（9-PhE）, 1-hydroxypyrene（1-OhP）. The levels of SAM and SAh in plasma were detected by hPLC-ultraviolet, and the expression level of h19 was detected by RT-PCR. The protein expression levels of SAhh and DNMT1 were detected by Western blot. The content of 8-OhdG and DNMT1 activity were detected by *** interaction between h19 and SAhh was detected by rna Binding ProteinImmunoprecipitation Assay. The interaction between SAhh and DNMT1 was detected by co-immunoprecipitation. The localization between h19, SAhh and DNMT1 was observed by lnc rna fluorescence in situ hybridization（FISh） combined with laser scanning confocal *** methylation level of OGG1 gene was detected by pyrosequencing, and the cell cycle was detected by flow cytometry. RESULTS After adjusting for covariates, urinary 1-hydroxypyrene（1-OhP） levels were positively associated with blood h19 rna expression（OR: 1.51, 95% CI: 1.03-2.19）, while were negatively associated with plasma SAhh activity（OR: 0.63, 95% CI: 0.41-0.98）. h19 binding to SAhh exaggerate DNA methyltransferase 1（DNMT1） expressions and activity with BaP *** of h19 enhanced the interaction of SAhh and DNMT1 induced by BaP. Although BaPtreated cells h19 single knockdown expectedly decreased OGG1 methylation, reduced oxidative DNA damage and recovered S phase arrest with altering SAhh and DNMT1, while SAhh or DNMT1 single knockdown shows the opposite trend. And the h19/SAhh double knockdown restored OGG1 methylation, oxidative DNA damage and S phase to the control level while SAhh/DNMT1 double knockdown aggravated the alteration. CONCLUSI

关键词： Polycyclic aromatic hydrocarbons Oxidative DNA damage 8-oxoguanine DNA glycosylase 1 long non-coding rna h19 S-adenosylhomocysteine hydrolase DNA methyltransferase

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