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Identifier uch.biology.msc//2003kirmizi
Title Μελέτη της μορφολογίας και γονιδιακής ρύθμισης στο συκώτι του ηπατοειδικά επαγόμενoυ HNF4 KO ενήλικου ποντικιού
Creator Kirmizi, Irini
Abstract The liver-enriched transcription factors are part of a complex transcriptional network, which seems to be responsible for both the determination and the maintenance of the hepatic phenotype. This network is established by a number of autoregulary and cross-regulatory pathways securing balanced high levels of the main factors in hepatocytes. Hepatocyte nuclear factor-4α (HNF4α) has been considered to be at the top of the hierarchy of the transcription factor cascade that drives hepatocyte differentiation. In addition, studies on the recently developed liver-specific HNF4 KO mice revealed the crucial role of this factor in the regulation of genes involved in key metabolic pathways of the adult liver. Using the liver-specific HNF4 KO mice we demonstrate that HNF4 is essential for the maintenance of normal liver architecture. In the absence of HNF4 the liver parenchyma is highly disorganized, and cell to cell contact is disrupted. Hepatocytes at the central vein areas are hypertrophic, while hepatocytes at throughout the liver lobule are vacuolated and accumulate lipids. Analysis of the expression pattern of other regulators involved in the in the liver specific transcriptional network revealed major defects in the transcription factor cross-regulatory pathways. Of particular interest is the reciprocal down and upregulation of HNF1α and HNF1-β respectively. Downregulation of HNF1α was expected as it is a known HNF4 target gene. On the other hand upregulation of HNF1-β in hepatocytes was surprising, as this gene is silent in adult parenchymal hepatocytes and its regulation has been thought to be independent of HNF4. This finding suggests that HNF4 expression directly or indirectly is involved in the activation of the HNF1-β gene during normal hepatocyte development.
Issue date 2003-11-01
Date available 2003-11-25
Collection   School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/6/b/b/metadata-dlib-2003kirmizi.tkl Bookmark and Share
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