1. Knockout of Purinergic P2Y 6 Receptor Fails to Improve Liver Injury and Inflammation in Non-Alcoholic Steatohepatitis.
- Author
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Nishiyama, Kazuhiro, Ariyoshi, Kohei, Nishimura, Akiyuki, Kato, Yuri, Mi, Xinya, Kurose, Hitoshi, Kim, Sang Geon, and Nishida, Motohiro
- Subjects
NON-alcoholic fatty liver disease ,FATTY liver ,LIVER injuries ,PURINERGIC receptors ,GENE expression ,G protein coupled receptors ,ASPARTATE aminotransferase - Abstract
Nonalcoholic steatohepatitis (NASH) is a disease that progresses from nonalcoholic fatty liver (NAFL) and which is characterized by inflammation and fibrosis. The purinergic P2Y
6 receptor (P2Y6 R) is a pro-inflammatory Gq /G12 family protein-coupled receptor and reportedly contributes to intestinal inflammation and cardiovascular fibrosis, but its role in liver pathogenesis is unknown. Human genomics data analysis revealed that the liver P2Y6 R mRNA expression level is increased during the progression from NAFL to NASH, which positively correlates with inductions of C-C motif chemokine 2 (CCL2) and collagen type I α1 chain (Col1a1) mRNAs. Therefore, we examined the impact of P2Y6 R functional deficiency in mice crossed with a NASH model using a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Feeding CDAHFD for 6 weeks markedly increased P2Y6 R expression level in mouse liver, which was positively correlated with CCL2 mRNA induction. Unexpectedly, the CDAHFD treatment for 6 weeks increased liver weights with severe steatosis in both wild-type (WT) and P2Y6 R knockout (KO) mice, while the disease marker levels such as serum AST and liver CCL2 mRNA in CDAHFD-treated P2Y6 R KO mice were rather aggravated compared with those of CDAHFD-treated WT mice. Thus, P2Y6 R may not contribute to the progression of liver injury, despite increased expression in NASH liver. [ABSTRACT FROM AUTHOR]- Published
- 2023
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