We evaluated the IGF1 system in cholangiocytes of primay biliary cirrhosis (PBC) patients and investigated the relationships with apoptosis. Biopsies of PBC patients (n=32) and normal subjects (n=5) were investigated by immunohistochemistry for expression in cholangiocytes of IGF1, IGF1-R, pAKT, terminal deoxynucleotide transferase end labeling (TUNEL), Bax (proapoptotic protein), and Bc12 (antiapoptotic protein). Whereas normal cholangiocytes were almost negative, cholangiocytes of PBC patients showed strong IHC staining for IGF1, IGF1-R, and pAKT, which increases from stage I to stage IV, where > 70% of cholangiocytes were positive. Bax/Bcl2 ratio reached the highest value (4.6) in PBC stage III when apoptosis is maximal (24% TUNEL positivity), whereas it declines in stage IV (1.4) when only 7.8% cholangiocytes were TUNEL positive. In PBC stages III and IV, expression of IGF1, IGF1-R, and pAKT in cholangiocytes was directly correlated with the antiapoptotic Bcl2 and inversely correlated with proapoptotic Bax, Bax/Bcl2 ratio, and TUNEL positivity. In conclusion, cholangiocytes of PBC patients showed a marked increase in IGF1, IGF1-R, and pAKT expression involving most cholangiocytes surviving in the terminal ductopenic stage. This was associated and correlated with a balance of pro- and antiapoptotic proteins favoring survival rather than apoptosis, suggesting a major role of IGF1 system in promoting cholangiocyte survival.
|Tipologia:||Articolo su rivista|
|Citazione:||Nori, P., Alvaro, D., Floreani, A., Mancino, M., Franchitto, A., Guido, M., et al. (2007). Activation of the IGF1 system characterizes cholangiocyte survival during progression of primary biliary cirrhosis. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 55(4), 327-334.|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||10.1369/jhc.6R7125.2006|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2007|
|Titolo:||Activation of the IGF1 system characterizes cholangiocyte survival during progression of primary biliary cirrhosis|
|Autori interni:||ANGELICO, MARIO|
|Autori:||Nori, P; Alvaro, D; Floreani, A; Mancino, M; Franchitto, A; Guido, M; Carpino, G; De Santis, A; Angelico, M; Attili, AF; Gaudio, E|
|Appare nelle tipologie:||01 - Articolo su rivista|
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