{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:32:34Z","timestamp":1789637554461,"version":"4.0.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2007,4,1]],"date-time":"2007-04-01T00:00:00Z","timestamp":1175385600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Histochem Cytochem."],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:p>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 Bcl2 (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 &gt;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.<\/jats:p>","DOI":"10.1369\/jhc.6r7125.2006","type":"journal-article","created":{"date-parts":[[2006,12,12]],"date-time":"2006-12-12T22:50:16Z","timestamp":1165963816000},"page":"327-334","source":"Crossref","is-referenced-by-count":36,"title":["Activation of the IGF1 System Characterizes Cholangiocyte Survival During Progression of Primary Biliary Cirrhosis"],"prefix":"10.1177","volume":"55","author":[{"given":"Paolo","family":"Onori","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Alvaro","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Division of Gastroenterology University of Rome, La Sapienza, 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