G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes

Wei, Xiaoli; Yin, Fang‐Fang; Wu, Miaomiao; Zhao, Xueqin; Zhu, Cheng; Xie, Ruiqian; Chen, Chongqing; Liu, Menghua; Ren, Ruixue; Kang, Guijie; Zhu, Chenwen; Cong, Jingjing; Wang, Hua; Wang, Xuefu

doi:10.1016/j.apsb.2022.10.011

Cited by 14 publications

(6 citation statements)

References 58 publications

(86 reference statements)

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“…Whether this may be related to the release of oxidised DNA fragments [30][31] is uncertain but may warrant investigation. Most recently, use of wild type and GPR35 knock-out mice has indicated that kynurenic acid can limit the development of high-fat-diet induced non-alcoholic steatohepatitis (NASH) [32]. Although this once more does not define that kynurenic acid is the only or indeed most important endogenous activator of GPR35, these studies are consistent with the potential of agonists of GPR35 to be useful in treating fatty liver diseases, including NASH [33] (Figure 1A).…”

Section: Use Of Kynurenic Acid In Rodent Modelsmentioning

confidence: 69%

“…Initially founded on studies that showed that lodoxamide was able to limit lipid accumulation induced by exposure to a liver X-receptor activator in human Hep3B hepatoma cells [63] there has been growing interest in the idea that agonism of GPR35 may be a useful approach to treat diseases linked to 'fatty liver' [32][33]. Surprisingly, however, Nam et al, [63] also showed that low concentrations of lodoxamide were able to replicate this effect in primary hepatocytes from wild type mice in a manner that was prevented, in a concentrationdependent fashion, by the human GPR35 specific antagonist CID2745687.…”

Section: Fatty Liver Diseasementioning

confidence: 99%

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GPR35: from enigma to therapeutic target

Milligan

2023

Trends in Pharmacological Sciences

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Section: Use Of Kynurenic Acid In Rodent Modelsmentioning

confidence: 69%

Section: Fatty Liver Diseasementioning

confidence: 99%

GPR35: from enigma to therapeutic target

Milligan

2023

Trends in Pharmacological Sciences

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“…In order to verify the function of these genes in ALF, relevant literature was searched and summarized in Table 1 . We found that CYP7A1 , LSS , SREBF1 , FASN are down-regulated and mainly participate in the synthesis of cholesterol in two species [ 29 – 32 ]. This suggests that cell damage caused by APAP is reflected in the obstruction of cholesterol synthesis in liver cells.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of gene expression between mice and humans in acetaminophen-induced liver injury by integrating bioinformatics analysis

Zhao,

Feng,

Zhang

et al. 2024

BMC Med Genomics

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Objective Mice are routinely utilized as animal models of drug-induced liver injury (DILI), however, there are significant differences in the pathogenesis between mice and humans. This study aimed to compare gene expression between humans and mice in acetaminophen (APAP)-induced liver injury (AILI), and investigate the similarities and differences in biological processes between the two species. Methods A pair of public datasets (GSE218879 and GSE120652) obtained from GEO were analyzed using “Limma” package in R language, and differentially expressed genes (DEGs) were identified, including co-expressed DEGs (co-DEGs) and specific-expressed DEGS (specific-DEGs). Analysis of Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed analyses for specific-DEGs and co-DEGs. The co-DEGs were also used to construct transcription factor (TF)-gene network, gene-miRNA interactions network and protein-protein interaction (PPI) network for analyzing hub genes. Results Mouse samples contained 1052 up-regulated genes and 1064 down-regulated genes, while human samples contained 1156 up-regulated genes and 1557 down-regulated genes. After taking the intersection between the DEGs, only 154 co-down-regulated and 89 co-up-regulated DEGs were identified, with a proportion of less than 10%. It was suggested that significant differences in gene expression between mice and humans in drug-induced liver injury. Mouse-specific-DEGs predominantly engaged in processes related to apoptosis and endoplasmic reticulum stress, while human-specific-DEGs were concentrated around catabolic process. Analysis of co-regulated genes reveals showed that they were mainly enriched in biosynthetic and metabolism-related processes. Then a PPI network which contains 189 nodes and 380 edges was constructed from the co-DEGs and two modules were obtained by Mcode. We screened out 10 hub genes by three algorithms of Degree, MCC and MNC, including CYP7A1, LSS, SREBF1, FASN, CD44, SPP1, ITGAV, ANXA5, LGALS3 and PDGFRA. Besides, TFs such as FOXC1, HINFP, NFKB1, miRNAs like mir-744-5p, mir-335-5p, mir-149-3p, mir-218-5p, mir-10a-5p may be the key regulatory factors of hub genes. Conclusions The DEGs of AILI mice models and those of patients were compared, and common biological processes were identified. The signaling pathways and hub genes in co-expression were identified between mice and humans through a series of bioinformatics analyses, which may be more valuable to reveal molecular mechanisms of AILI.

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“…The latter promotes an increase in glycolytic flux and promotes glucose uptake and metabolism in skeletal muscle. That is, TGR5 regulates blood glucose balance by increasing blood glucose clearance in skeletal muscle and effectively improves muscle insulin resistance 167 , 168 . GLP-1 induced by TGR5 also improves insulin resistance in skeletal muscle.…”

Section: Mechanism Of Action Of Tgr5 In Obesitymentioning

confidence: 99%

Mechanism of action of the bile acid receptor TGR5 in obesity

Lun,

Yan,

Guo

et al. 2024

Acta Pharmaceutica Sinica B

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G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes

Cited by 14 publications

References 58 publications

GPR35: from enigma to therapeutic target

GPR35: from enigma to therapeutic target

Comparative analysis of gene expression between mice and humans in acetaminophen-induced liver injury by integrating bioinformatics analysis

Mechanism of action of the bile acid receptor TGR5 in obesity

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