Transcriptomic landscapes of effective and failed liver regeneration in humans.

Patrick Starlinger,Laura Brunnthaler,Chantal McCabe,David Pereyra,Jonas Santol, Jessica Steadman,Matthias Hackl,Susanna Skalicky,Hubert Hackl,Raphael Gronauer,Daniel O'Brien,Renate Kain,Petra Hirsova,Gregory J Gores,Chen Wang,Thomas Gruenberger,Rory L Smoot,Alice Assinger

JHEP reports : innovation in hepatology（2023）

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摘要

Using a unique human biorepository, focused on liver regeneration (LR), we explored the landscape of circulating and tissue-level alterations associated with both functional and dysfunctional LR. In contrast to experimental animal models, people with dysfunctional LR demonstrated an aggravated transcriptional inflammatory response, higher intracellular adhesion molecule-1 (ICAM-1) induction, intrahepatic neutrophil accumulation and activation upon induction of LR. Although inflammatory responses appear rapidly after liver resection, people with dysfunctional LR have exaggerated inflammatory responses that appear to be related to decreased levels of LSEC DUSP4, challenging existing concepts of post-resectional LR.

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关键词

ALT, alanine aminotransferase,AST, aspartate aminotransferase,CASH, chemotherapy associated steatohepatitis,DLR, dysfunctional LR,DUSP-4,DUSP4, dual-specificity phosphatase 4,FDR, false discovery rate,FLR, functional LR,FPKM, fragments per kilobase of transcript per million mapped reads,Human,ICAM-1, intracellular adhesion molecule-1,IPA, Ingenuity Pathway Analysis,IVCL, inferior vena cava ligation,Inflammation,LPS, lipopolysaccharide,LR, liver regeneration,LSEC, liver sinusoidal endothelial cell,Liver regeneration,MFI, mean fluorescence intensity,MPO, myeloperoxidase,NASH, non-alcoholic steatohepatitis,Neutrophils,PCA, principal component analysis,POD1, 1 day after liver resection,POD5, 5 days after liver resection,STRING, Search Tool for the Retrieval of Interacting Genes/Proteins,TMM, trimmed mean of M values,TNF, tumour necrosis factor,logCPM, log counts per million,pTPM, protein-coding transcripts per million

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