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Transcription networks in liver development and acute liver failure

Liver Research 2023年第1期7卷 47-55页

作者： Rilu Feng Roman Liebe Hong-Lei Weng Department of Medicine II Section Molecular HepatologyUniversity Medical Center MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany Clinic of Gastroenterology Hepatology and Infectious DiseasesHeinrich Heine UniversityDüsseldorfGermany Department of Medicine II Saarland University Medical CentreSaarland UniversityHomburgGermany

Acute liver failure(ALF)is a medical emergency due to massive hepatocyte *** such a harsh condition,maintaining transcriptional regulation in the remaining hepatocytes while activating similar transcription factor networks in liver progenitor cells(LPCs)to ensure essential liver functions are two critical processes to rescue patients from liver failure and *** this review,we discuss the formation and functions of transcription networks in ALF and liver *** focus on a hierarchical network of transcription factors that responds to different pathophysiological circumstances:(1)Under normal circumstances,pioneer factor forkhead box protein A2(FOXA2)coordinates several constitutive hepatic transcription factors,such as hepatic nuclear factor 4 alpha(HNF4a)and CCAAT-enhancer binding protein a(C/EBPa),which ensure normal liver function;(2)When the expression of both HNF4a and C/EBPa in hepatocytes are disrupted by severe inflammation,retinoic acid receptor(RAR)is the alternative transcription factor that compensates for their absence;(3)When massive hepatic necrosis occurs,a similar transcription network including FOXA2 and HNF4a,is activated as a“rescue network”in LPCs to maintain vital liver functions when hepatocytes fail,and thus ensures *** of these master transcription factors in hepatocytes and LPCs is tightly regulated by hormone signals and *** performance of this hierarchical transcription network,in particularly the“rescue network”described above,significantly affects the clinical outcome of ALF.

关键词： Pioneer transcription factor Lineage-determining transcription factor Signal-driven transcription factor Hepatocyte massive hepatic necrosis Liver progenitor cell

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