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Cadamuro, Massimiliano (2008) Patogenesi molecolare delle malattie disembriogenetiche dell'epitelio bibliare. [Ph.D. thesis]

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Abstract (english)

The aim of this thesis was to investigate different malformative cholangiopathies due to specific genetic defects and characterised by differen biliary lesions, and analyse the molecular factors involved in the pathogenesis of these cholangiopathies to characterise a molecular link between these molecular factors and the genetic defect; finally, I have evaluated if these factors could influence the clinical progression of these cholangiopathies. This thesis was divided in three studies:
Study # 1. Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases
Study # 2. Analysis of liver repair mechanisms in Alagille syndrome and biliary atresia reveals a role for notch signaling
Study # 3. Epithelial expression of angiogenic growth factors modulate arterial vasculogenesis in human liver development.
In the study # 1 I have shown that an aberrant overexpreesion of angiogenic factors (VEGF, VEGFR-1, VEGFR-2, Ang-1 Ang-2 e Tie-2) by the hepatic epithelial cells of the ADPKD is responsible for the autocrine overgrowth of the cystic epithelium and of the increased extension of the pericystic vascular plexus of the biliary cysts.
In the study # 2 I have showd that during the foetal liver ontogenesis, the expression of these angiogenic growth factors by biliary epithelial cells is responsible for the coordinated growth of bile ducts and hepatic arteries.
In the study # 3 I have demonstrated that lacking of the Jagged1/Notch2 signal pathway induce the accumulation of intermediate epato-biliary cells (IHBC) that cannot develop to reactive ductular cells, conversely to the biliary atresia, characterised by the activation of the progenitor cells compartement and by a huge ductular reaction. This ductular reaction is the pacemaker of the portal fibrosis in the cholestatic cholangiopathies and is responsible for the higher aggressivity of the biliary atresia respect to the Alagille's syndrome.


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EPrint type:Ph.D. thesis
Tutor:Okolicsanyi, Lajos and Strazzabosco, Mario
Ph.D. course:Ciclo 20 > Scuole per il 20simo ciclo > BIOLOGIA E MEDICINA DELLA RIGENERAZIONE > SCIENZE EPATOLOGICHE E GASTROENTEROLOGICHE
Data di deposito della tesi:26 January 2008
Anno di Pubblicazione:26 January 2008
Key Words:ADPKD, Sindrome di Alagille, atresia biliare, colangiocita, dotti biliari, sviluppo fetale epatico
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/12 Gastroenterologia
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Scienze Chirurgiche Gastroenterologiche "Pier Giuseppe Cevese"
Codice ID:437
Depositato il:05 Sep 2008
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