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TLR4 Knockout Attenuates BDL-induced Liver Cholestatic Injury through Amino Acid and Choline Metabolic Pathways

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Summary

The exact mechanism by which knockout of Toll-like receptor 4 (TLR4) attenuates the liver injury remains unclear. The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation (BDL)-induced liver cholestatic injury and the underlying mechanism. Wild type (WT) mice and TLR4 knockout (TLR4-KO) mice were used for the establishment of the BDL model. Metabolomics were applied to analyze the changes of small molecular metabolites in the serum and liver of the two groups. The serum biochemical indexes and the HE staining results of liver tissue showed that liver damage was significantly reduced in TLR4-KO mice after BDL when compared with that in WT mice. The metabolite analysis results showed that TLR4 KO could maintain the metabolisms of amino acids- and choline-related metabolites. After BDL, the amino acids- and choline-related metabolites, especially choline and 3-hydroxybutyrate, were significantly increased in WT mice (both in serum and liver), but these metabolites in the liver of TLR4-KO mice after BLD were not significant different from those before BLD. In conclusion, TLR4 KO could attenuate BDL-induced liver cholestatic injury through regulating amino acid and choline metabolic pathways.

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Authors and Affiliations

  1. Department of General Surgery, Jiangxi Provincial Children’s Hospital, Nanchang, 330006, China

    Shou-hua Zhang, Yu Xiao, Jun Lei & Wei-long Chen

  2. Department of Ophthalmology, Jiangxi Provincial Children’s Hospital, Nanchang, 330006, China

    Yong Chai

  3. Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China

    Meng-jie Yu

  4. Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

    Jin-long Yan, Jia-le Yang & Xin Yu

  5. Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, 330006, China

    Ju-hua Xiao

Authors
  1. Shou-hua Zhang
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  2. Meng-jie Yu
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  3. Jin-long Yan
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  4. Ju-hua Xiao
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  5. Yu Xiao
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  7. Jun Lei
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  8. Xin Yu
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  9. Wei-long Chen
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  10. Yong Chai
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Corresponding author

Correspondence to Yong Chai.

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The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

Additional information

This study was supported by the National Natural Science Foundation of China (Nos. 81960101; 81860483).

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Zhang, Sh., Yu, Mj., Yan, Jl. et al. TLR4 Knockout Attenuates BDL-induced Liver Cholestatic Injury through Amino Acid and Choline Metabolic Pathways. CURR MED SCI 41, 572–580 (2021). https://doi.org/10.1007/s11596-021-2364-8

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  • DOI: https://doi.org/10.1007/s11596-021-2364-8

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