Expression of toll-like receptors in hepatic cirrhosis and hepatocellular carcinoma

Sun, Lin; Dai, Jingjing; Hu, Wen-Kui; Wang, J

doi:10.4238/gmr.15027419

Cited by 32 publications

(24 citation statements)

References 36 publications

(37 reference statements)

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“…As previously described, even in this tolerant environment, liver MΦ are able to respond to the detection of specific pathogens . Liver MΦ express a large spectrum of PRR, among which, TLR1/2, TLR2/6, TLR3, TLR4, TLR8 and RIGI/MDA5, leading, after stimulation, to the secretion of a large spectrum of immune factors such as ROS, cytokines (IL‐6, IL‐10, IL‐12, TNFα…) and chemokines (CCL3, CCL5…) among others . Liver MΦ have also been described to be functional for several inflammasomes (AIM2, NLRP3), which, upon stimulation, induce the production, maturation and secretion of IL‐1β and IL‐18 .…”

Section: Introductionmentioning

confidence: 88%

Liver macrophages: Friend or foe during hepatitis B infection?

Faure-Dupuy

Durantel

Lucifora

2018

Liver International

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Section: Introductionmentioning

confidence: 88%

Liver macrophages: Friend or foe during hepatitis B infection?

Faure-Dupuy

Durantel

Lucifora

2018

Liver International

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“…It is well known that TLR4 signaling plays a pivotal role in liver inflammation and fibrosis. Therefore, targeting TLR4 signaling pathways represents an attractive strategy for liver fibrosis treatment (32). In this study, our data portrayed that differentially expressed KDM4D modulated TLR4 level in HSCs by modulating chromatin structure.…”

Section: Discussionmentioning

confidence: 72%

The Histone Demethylase KDM4D Promotes Hepatic Fibrogenesis by Modulating Toll-Like Receptor 4 Signaling Pathway

Dong

Jiang

et al. 2018

Preprint

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Potential conflict of interest: Nothing to report.Abbreviations: HSC, hepatic stellate cell; H3K9, histone H3 on lysine 9; TLR4, Toll-like receptor 4; α-SMA, α-smooth muscle actin; KMT, lysine methyltransferase; KDM, lysine demethylase; KDM4, lysine (K)-specific demethylase 4; qRT-PCR, quantitative real-time PCR; siRNA, small interfering RNA; FBS, fetal bovine serum; i.p., intraperitoneally; CCl 4 , carbon tetrachloride; TAA, thioacetamide; BDL, bile duct ligation; AAV, adeno-associated virus;shRNA, short-hairpin RNA; ALT, alanine aminotransferase; H&E, hematoxylin-eosin; ChIP, chromatin immunoprecipitation; DMEM, Dulbecco's Modified Eagle's Medium; H3K9me2, histone di-methyl-H3K9; IHC, immunohistochemistry; NF-κB, nuclear factor kappa B; MyD88, myeloid differentiation factor 88; GFP, green fluorescent protein.3 AbstractAccumulating evidence has revealed the pivotal role of epigenetic regulation in the pathogenesis of liver disease. However, the epigenetic mechanism that accounts for hepatic stellate cells (HSCs) activation in liver fibrosis remains largely unknown. In this study, primaryHSCs were used to screen the differentially expressed histone H3 lysine methyltransferases and demethylases during HSC activation. KDM4D was identified as a remarkable upregulated histone H3 demethylase during HSC activation. The overexpression profile of KDM4D was further confirmed in three fibrosis animal models and human fibrotic liver tissues. In vitro genetic silencing of Kdm4d impaired the collagen gel contraction and migration capacity of primary HSCs. In established CCl 4 -induced mice model, Kdm4d knockdown inhibited fibrosis progression, and promoted fibrosis reversal, with enhanced thinning and splitting of fibrotic septa, as well as a dramatic decrease in collagen area. Whole gene transcriptome analysis showed the regulatory role of KDM4D in Toll-Like Receptor (TLR) signaling pathway. Mechanistically, KDM4D catalyzed histone 3 on lysine 9 (H3K9) di-, and tri-demethylation, which promoted TLR4 expression, and subsequently prompted liver fibrogenesis by activating NF-κB signaling pathways. Conclusion: KDM4D facilitates TLR4 transcription through demethylation of H3K9, thus activating TLR4/NF-κB signaling pathways in HSCs, contributing to HSC activation and collagen crosslinking, further, hepatic fibrosis progression.

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“…Therefore, the impact of TLR3 polymorphisms may act in an ethnic- and viral-specific manner. At the cellular and molecular level, there is a growing body of evidence indicating that TLR3 plays a role in cirrhosis pathogenesis and hepatocarcinogenesis [42, 43]. For example, it has been documented that dsRNA activates TLR3 which subsequently results in NK cell accumulation and activation leading to liver inflammation.…”

Section: Discussionmentioning

confidence: 99%

Association of Toll-Like Receptor 3 Single-Nucleotide Polymorphisms and Hepatitis C Virus Infection

Al-Anazi

Matou‐Nasri

Abdo

et al. 2017

Journal of Immunology Research

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Toll-like receptor 3 (TLR3) plays a key role in innate immunity by recognizing pathogenic, double-stranded RNAs. Thus, activation of TLR3 is a major factor in antiviral defense and tumor eradication. Although downregulation of TLR3 gene expression has been mainly reported in patients infected with hepatitis C virus (HCV), the influence of TLR3 genotype on the risk of HCV infection, HCV-related cirrhosis, and/or hepatocellular carcinoma (HCC) remains to be determined. Single-nucleotide polymorphisms (SNPs) within the TLR3 gene and their associations with HCV-related disease risk were investigated in a Saudi Arabian population in this study. Eight TLR3 SNPs were analyzed in 563 patients with HCV, which consisted of 437 patients with chronic HCV infections, 88 with HCV-induced liver cirrhosis, and 38 with HCC. A total of 599 healthy control subjects were recruited to the study. Among the eight TLR3 SNPs studied, the rs78726532 SNP was strongly associated with HCV infection when compared to that in healthy control subjects. The rs5743314 was also strongly associated with HCV-related liver disease progression (cirrhosis and HCC). In summary, these results indicate that distinct genetic variants of TLR3 SNPs are associated with HCV infection and HCV-mediated liver disease progression in the Saudi Arabian population.

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Expression of toll-like receptors in hepatic cirrhosis and hepatocellular carcinoma

Cited by 32 publications

References 36 publications

Liver macrophages: Friend or foe during hepatitis B infection?

Liver macrophages: Friend or foe during hepatitis B infection?

The Histone Demethylase KDM4D Promotes Hepatic Fibrogenesis by Modulating Toll-Like Receptor 4 Signaling Pathway

Association of Toll-Like Receptor 3 Single-Nucleotide Polymorphisms and Hepatitis C Virus Infection

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