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Proc Natl Acad Sci U S A. 2011 Apr 19;10816:6626 31. Epub 2011 Apr 4. Hyperactivation of anandamide synthesis and law of cell cycle progression via cannabinoid type 1 CB1 receptors within the regenerating liver. The mammalian liver regenerates upon tissue loss, which induces quiescent hepatocytes case study enter the cell cycle and submit to limited replication under the manage of numerous hormones, increase factors, and cytokines. Endocannabinoids performing via cannabinoid type 1 receptors CB1R advertise neural progenitor cell proliferation, and in the liver they advertise lipogenesis. These findings imply the involvement of CB1R within the control of liver regeneration. In the present study, researchers file that mice missing CB1R globally or in hepatocytes only and wild type mice treated with a CB1R antagonist have a delayed proliferative response case study two thirds partial hepatectomy PHX. In wild type mice, PHX leads case study increased hepatic expression of CB1R and hyperactivation of the biosynthesis of the endocannabinoid anandamide within the liver via an in vivo pathway regarding conjugation of arachidonic acid and ethanolamine by fatty acid amide hydrolase. In wild type but not CB1R / mice, PHX induces robust up law of key cell cycle proteins concerned in mitotic progression, adding cyclin dependent kinase 1 Cdk1, cyclin B2, and their transcriptional regulator forkhead box protein M1 FoxM1, as revealed by ultrahigh throughput RNA sequencing and pathway analysis and proven by real time PCR and Western blot analyses. Treatment of untamed type mice with anandamide induces identical changes mediated via activation of the PI3K/Akt pathway.
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