Abstract BACKGROUND: In different cell types, the insulin-like growth factor 1 and its receptor modulate growth, apoptosis and damage repair in cooperation with estrogen receptors. AIM: To evaluate the involvement of the insulin-like growth factor 1 system and estrogen receptors in bile salts modulation of apoptosis/proliferation of hepatocytes and cholangiocytes. Primary cultures of rat hepatocytes and cholangiocytes were exposed to glycochenodeoxycholate or tauro-CDC in the presence or absence of insulin-like growth factor 1 receptor blocking antibody (alphaIR3), small interfering RNA for insulin-like growth factor 1, 17beta-estradiol or estrogen receptor antagonist (ICI 182,780). Proliferation was evaluated by proliferating cell nuclear antigen Western blot and apoptosis by measuring caspase-3 activity or annexin-V. RESULTS: In hepatocytes, the insulin-like growth factor 1 receptor blocker enhanced glycochenodeoxycholate-induced apoptosis and caused tauro-CDC to promote apoptosis. 17Beta-estradiol or the estrogen receptor antagonist (ICI 182,780) did not influence the apoptotic effect of glycochenodeoxycholate. In cholangiocytes, both glycochenodeoxycholate and tauro-CDC induced proliferation at 100microM, while they induced apoptosis at 1mM with a more pronounced effect of glycochenodeoxycholate. Apoptosis induced by 1mM glycochenodeoxycholate or tauro-CDC in cholangiocytes was enhanced by blocking insulin-like growth factor 1 receptor or by silencing insulin-like growth factor 1. 17Beta-estradiol counteracts glycochenodeoxycholate-induced cholangiocyte apoptosis by enhancing insulin-like growth factor 1 secretion and activating the insulin-like growth factor 1 system. CONCLUSIONS: Modulation of the IGF1 system could represent a potential strategy for the management of bile salts-induced liver injury.
Bile salts regulate proliferation and apoptosis of liver cells by modulating the IGF1 system / DRUDI METALLI, V; Mancino, MARIA GRAZIA; Mancino, A; Torrice, Alessia; Gatto, M; Attili, Adolfo Francesco; Alpini, G; Alvaro, Domenico. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1590-8658. - STAMPA. - 39:7(2007), pp. 654-662. [10.1016/j.dld.2007.03.008]
Bile salts regulate proliferation and apoptosis of liver cells by modulating the IGF1 system
MANCINO, MARIA GRAZIA;TORRICE, Alessia;ATTILI, Adolfo Francesco;ALVARO, Domenico
2007
Abstract
Abstract BACKGROUND: In different cell types, the insulin-like growth factor 1 and its receptor modulate growth, apoptosis and damage repair in cooperation with estrogen receptors. AIM: To evaluate the involvement of the insulin-like growth factor 1 system and estrogen receptors in bile salts modulation of apoptosis/proliferation of hepatocytes and cholangiocytes. Primary cultures of rat hepatocytes and cholangiocytes were exposed to glycochenodeoxycholate or tauro-CDC in the presence or absence of insulin-like growth factor 1 receptor blocking antibody (alphaIR3), small interfering RNA for insulin-like growth factor 1, 17beta-estradiol or estrogen receptor antagonist (ICI 182,780). Proliferation was evaluated by proliferating cell nuclear antigen Western blot and apoptosis by measuring caspase-3 activity or annexin-V. RESULTS: In hepatocytes, the insulin-like growth factor 1 receptor blocker enhanced glycochenodeoxycholate-induced apoptosis and caused tauro-CDC to promote apoptosis. 17Beta-estradiol or the estrogen receptor antagonist (ICI 182,780) did not influence the apoptotic effect of glycochenodeoxycholate. In cholangiocytes, both glycochenodeoxycholate and tauro-CDC induced proliferation at 100microM, while they induced apoptosis at 1mM with a more pronounced effect of glycochenodeoxycholate. Apoptosis induced by 1mM glycochenodeoxycholate or tauro-CDC in cholangiocytes was enhanced by blocking insulin-like growth factor 1 receptor or by silencing insulin-like growth factor 1. 17Beta-estradiol counteracts glycochenodeoxycholate-induced cholangiocyte apoptosis by enhancing insulin-like growth factor 1 secretion and activating the insulin-like growth factor 1 system. CONCLUSIONS: Modulation of the IGF1 system could represent a potential strategy for the management of bile salts-induced liver injury.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.