首页|Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

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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Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compound-based Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ 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 proteins.Real-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-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overex-pressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19 expression,STAT3 expression and STAT3 phosphorylation.This 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 HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphory-lation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC,thereby suppressing cell activation.

Liver cirrhosis,biliaryLong non-coding RNA H19Danhongqing formulaCholangiocyteHepatic stellate cellsSTAT3 transcription factor

Meng Li、Yang Zhou、Hui Zhu、Lie-ming Xu、Jian Ping

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Institute of Liver Diseases,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China

Preventive Treatment Center,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China

Department of Gastroenterology,Suzhou Traditional Chinese Medicine Hospital,Suzhou 215000,Jiangsu Province,China

Shanghai Key Laboratory of Traditional Chinese Medicine,Shanghai 201203,China

Key Laboratory of Liver and Kidney Diseases(Ministry of Education),Shanghai 201203,China

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国家自然科学基金Project of Science and Technology Commission of Shanghai Municipality

8177398015401902600

2024

10.1016/j.joim.2024.03.006

结合医学学报(英文版)
上海市中西医结合学会,上海长海医院

结合医学学报(英文版)

CSTPCD
影响因子：0.711
ISSN：2095-4964
年,卷(期)：2024.22(2)
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