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.

Activation of the IGF1 system characterizes cholangiocyte survival during progression of primary biliary cirrhosis / Onori, Paolo; Alvaro, Domenico; A. R., Floreani; M. G., Mancino; Franchitto, Antonio; M., Guido; G., Carpino; DE SANTIS, Adriano; Mario, Angelico; Attili, Adolfo Francesco; Gaudio, Eugenio. - In: JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY. - ISSN 0022-1554. - STAMPA. - 55:4(2007), pp. 327-334. [10.1369/jhc.6r7125.2006]

Activation of the IGF1 system characterizes cholangiocyte survival during progression of primary biliary cirrhosis

ONORI, PAOLO;ALVARO, Domenico;FRANCHITTO, Antonio;G. Carpino;DE SANTIS, Adriano;ATTILI, Adolfo Francesco;GAUDIO, EUGENIO
2007

Abstract

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.
2007
cholestasis; apoptosis; primary biliary cirrhosis; primary biliary cirrhosis igf1 cholangiocytes apoptosis cholestasis; cholangiocytes; igf1
01 Pubblicazione su rivista::01a Articolo in rivista
Activation of the IGF1 system characterizes cholangiocyte survival during progression of primary biliary cirrhosis / Onori, Paolo; Alvaro, Domenico; A. R., Floreani; M. G., Mancino; Franchitto, Antonio; M., Guido; G., Carpino; DE SANTIS, Adriano; Mario, Angelico; Attili, Adolfo Francesco; Gaudio, Eugenio. - In: JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY. - ISSN 0022-1554. - STAMPA. - 55:4(2007), pp. 327-334. [10.1369/jhc.6r7125.2006]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/366799
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