Farnesoid X Receptor Antagonizes JNK Signaling Pathway in Liver Carcinogenesis by Activating SOD3

Wang, Yandong; Chen, Weidong; Li, Cunbao; Guo, Cong; Li, Yanyan; Qi, Hui; Shen, Hailing; Kong, Jing; Long, Xuecheng; Yuan, Frank; Wang, Xichun; Huang, Wendong

doi:10.1210/me.2014-1225

Cited by 41 publications

(31 citation statements)

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“…Then cells were treated with IL-6 (20 ng/mL) for 6 hours. The cells were lysed for immunoblot analysis as reported previously [ 39 – 41 ]. Bands on blots were visualized using Tanon 5200 enhanced chemiluminescence (ECL) detection system (Tanon, China) and quantified with a computerized digital imaging system using Tanon software.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-149* suppresses hepatic inflammatory response through antagonizing STAT3 signaling pathway

Zhang

Wang

et al. 2017

Oncotarget

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Chronic inflammation is increasingly recognized as an important component of tumorigenesis and metabolic diseases. The roles of microRNA149* (miRNA149*) in inflammation remain poorly understood. Here, we demonstrate that miR-149* is a suppressor of STAT3-mediated inflammation. MiR-149*−/− mice were generated with CRISPR/CAS9 technique. In a lipopolysaccharide (LPS)-induced inflammation model, miR-149*−/− mice show more severe liver injury and inflammation, compared with wild-type (WT) mice. MiR-149*−/− mice also displayed elevated messenger RNA (mRNA) levels of interleukin (IL)-6, inducible nitric oxide synthase (iNOS), complement C3 (C3) and IL-4 in response to LPS. Then miR-149* agomir administration is largely able to alleviate the LPS-induced some inflammatory gene expression in WT mouse liver. In vitro, miR-149* mimics inhibited expression of STAT3-meidated inflammatory mediators induced by LPS and suppresses the phosphorylation of STAT3 and its transcription activity in HepG2 cells. These findings identify miR-149* as a negative mediator of inflammation that may serve as an attractive therapeutic tool for immune and inflammatory liver diseases.

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Section: Methodsmentioning

confidence: 99%

MicroRNA-149* suppresses hepatic inflammatory response through antagonizing STAT3 signaling pathway

Zhang

Wang

et al. 2017

Oncotarget

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“…After 24 h, cells were subjected to compound 1 or 2 at the concentration of 50 μM for another 24 h. Cells then treated with LPS (500 ng/ml) (Sigma, MO) for 12 h. Subsequently, cells were harvested and extracted for analysis. The quantifification of mRNA in macrophage cells was performed using a previously standardized method 21,22 .…”

Section: Concise Synthesis Of Compounds 1 Andmentioning

confidence: 99%

Isolation of two rare N-glycosides from Ginkgo biloba and their anti-inflammatory activities

Cheng

Guo

Cui

et al. 2020

Sci Rep

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two rare N-β-D-glucopyranosyl-1H-indole-3-acetic acid conjugates, N-[2-(1-β-D-glucopyranosyl)-1Hindol-3-yl)acetyl]-L-glutamic acid (1) and N-[2-(1-β-D-glucopyranosyl)-1H-indol-3-yl)acetyl]-L-aspartic acid (2) were isolated from Ginkgo biloba. The structures were elucidated by analyses of HRMS and NMR spectroscopic data. In addition, a simplified and efficient synthetic route for compounds 1 and 2 is also disclosed to determine the absolute configurations of them. This concise syntheses of compounds 1 and 2 may facilitate studies of the biology of this type alkaloids. Compounds 1 and 2 were also tested for their cytotoxic and anti-inflammatory activities. The biological evaluation showed that compounds 1 and 2 led to the decrease of interleukin (IL)-6, nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 at mRNA level in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells. Ginkgo biloba L., one of the most well-known medicinal plants worldwide, is considered as a living fossil due to its survival over millions of years 1. Pharmacological studies have shown that extracts from its leaves and seeds exhibit antiparasitic, antifungal, antibacterial and antiviral activities. G. biloba extracts have also found broad applications in the treatment of cognitive diseases 2-5. Since the discovery of ginkgolides A-C, a lot of phytochemical and pharmaceutical studies have been conducted on the G. biloba leaves 6-8. It is well known that G. biloba leaf extracts, mainly composed of ginkgolides, flavonoids and phenolic compounds, are frequently used in the treatment of cardiovascular, cerebrovascular, and neurological diseases 9,10. The dried seeds of G. biloba (called "baiguo" in Chinese), have been reported in the Chinese Pharmacopoeia as effective treatments for cough, asthma, enuresis, alcohol misuse, pyogenic skin infections and worm infestations in the intestinal tract 11,12. In contrast to extensive studies on G. biloba leaves, the seeds of G. biloba have received much less attention. In order to find structurally interesting and bioactive components from Ginkgo seeds and provide a better understanding of their functions, we conducted a phytochemical investigation of Ginkgo seeds. As a result, two N-β-D-glucopyranosyl-1H-indole-3-acetic acid conjugates were isolated from the title plant and the concise syntheses of 1 and 2 were also enclosed to determine the absolute configurations of compounds 1 and 2 (Fig. 1). Notably, compounds 1 and 2 are naturally isolated N-glycosides, which are rarely found in natural products. To the best of our knowledge, only very few examples have been reported previouly 13-17. Although compounds 1 and 2 were detected in an alkaline hydrolysate of rice extract using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) 18 , there are no examples of their isolation, absolute configurations determination and bioactivities. Reported herein are the structural identification, concise syntheses and bioactivities of them. Results and discussion Ginkgos...

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“…Nevertheless, our data suggest that the activation of JNK pathway by TAK1 leads to downregulation of transcription factor FXRα and in turn results in HBV suppression. Although FXRα activation by bile acids antagonizes the JNK signaling pathway in liver carcinogenesis34, the mechanism of JNK pathway regulation of FXRα requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor β-activated kinase 1 transcriptionally suppresses hepatitis B virus replication

Pang

Zhang

Lin

et al. 2017

Sci Rep

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Hepatitis B Virus (HBV) replication in hepatocytes is restricted by the host innate immune system and related intracellular signaling pathways. Transforming growth factor β-activated kinase 1 (TAK1) is a key mediator of toll-like receptors and pro-inflammatory cytokine signaling pathways. Here, we report that silencing or inhibition of endogenous TAK1 in hepatoma cell lines leads to an upregulation of HBV replication, transcription, and antigen expression. In contrast, overexpression of TAK1 significantly suppresses HBV replication, while an enzymatically inactive form of TAK1 exerts no effect. By screening TAK1-associated signaling pathways with inhibitors and siRNAs, we found that the MAPK-JNK pathway was involved in TAK1-mediated HBV suppression. Moreover, TAK1 knockdown or JNK pathway inhibition induced the expression of farnesoid X receptor α, a transcription factor that upregulates HBV transcription. Finally, ectopic expression of TAK1 in a HBV hydrodynamic injection mouse model resulted in lower levels of HBV DNA and antigens in both liver and serum. In conclusion, our data suggest that TAK1 inhibits HBV primarily at viral transcription level through activation of MAPK-JNK pathway, thus TAK1 represents an intrinsic host restriction factor for HBV replication in hepatocytes.

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Farnesoid X Receptor Antagonizes JNK Signaling Pathway in Liver Carcinogenesis by Activating SOD3

Cited by 41 publications

References 50 publications

MicroRNA-149* suppresses hepatic inflammatory response through antagonizing STAT3 signaling pathway

MicroRNA-149* suppresses hepatic inflammatory response through antagonizing STAT3 signaling pathway

Isolation of two rare N-glycosides from Ginkgo biloba and their anti-inflammatory activities

Transforming growth factor β-activated kinase 1 transcriptionally suppresses hepatitis B virus replication

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