60 research outputs found
A new regulator of mitochondrial OXPHOS in hepatocytes and HCC cell lines: the AAA plus ATPase RuvBL1
Nuclear orphan receptor COUP-TF2 induces anoikis resistance, amoeboid migration and metastatic potential in hepatocellular carcinoma (HCC)
Splenic diffuse red-pulp small B-cell lymphoma associated with hepatitis B virus: a report of two cases
Krüppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury
Kruppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)- treated mice. In mice with hepatocytespecific Klf6 knockout (DeltaKlf6), cell proliferation following partial hepatectomy (PHx) was increased compared to controls. Interestingly, key autophagic markers and mediators LC3-II, Atg7 and Beclin1 were reduced in DeltaKlf6 mice livers. Using luciferase assay and ChIP, KLF6 was established as a direct transcriptional activator of ATG7 and BECLIN1, but was dependent on the presence of p53. Here we show, that KLF6 expression is induced in ALF and in the regenerating liver, where it activates autophagy by transcriptional induction of ATG7 and BECLIN1 in a p53-dependent manner. These findings couple the activity of an important growth inhibitor in liver to the induction of autophagy in hepatocytes
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist
MiR-19a, miR-122 and miR-223 are differentially regulated by hepatitis B virus X protein and involve in cell proliferation in hepatoma cells
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581]
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