In Intrahepatic Cholestasis of Pregnancy (ICP) an accumulation of bile acids (BA) in the fetal compartment occurs. It is known that a BA efflux is induced by UDCA administration but the molecular basis of this transplacental transport is only partially defined. Aim of the present study was to determine if placental BCRP, able to transport BA, is regulated by UDCA in ICP. Methods: 14 pregnant women with ICP (6 untreated, 37.5±1.33 years; 8 treated with UDCA − 25 mg/kg/day, 32.14±2.16 years) and 7 agematched healthy controls (34.2±1.2 years) have agreed to participate to the study (none had gallstone disease, abnormal liver tests, liver steatosis on ultrasonography). Placentas were obtained at delivery and processed for membrane extraction. Protein expression was evaluated by standard immunoblotting techniques using actin as an internal control. Statistical differences between groups were evaluated by one way ANOVA with Dunn’s Multiple Comparison test. Results: BCRP was expressed only on the apical membrane of the syncytiotrophoblast. A significant difference was observed between the three groups (ANOVA, p = 0.01). BCRP expression was similar in cont rols and in the untreated ICP group. The administration of UDCA induced a significant increase in placental BCRP expression compared to controls (254.5±58.46 vs 100±8.002% of control, p<0.05). Conclusion: In this preliminary study we are able to confirm that BCRP is expressed only on the apical membrane of the syncytiotrophoblast. ICP treatment with high dose UDCA significantly up-regulates placental BCRP expression favouring BA transport towards the foetal compartment.
UDCA UP-REGULATES HUMAN PLACENTAL BCRP EXPRESSION: PRELIMINARY RESULTS / F. Azzaroli; M.E. Raspanti; F. Alessandrelli; V. Feletti; F. Buonfiglioli; P. Cecinato; M. Montagnani; A. Colecchia; D. Festi; E. Roda; G. Mazzella. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - ELETTRONICO. - 50:(2009), p. 657. (Intervento presentato al convegno Abstracts of the International Liver Congress TM 2009. 44th Annual Meeting of the European Association for the Study of the Liver tenutosi a Copenhagen, Denmark nel 22-26 April 2009).
UDCA UP-REGULATES HUMAN PLACENTAL BCRP EXPRESSION: PRELIMINARY RESULTS
AZZAROLI, FRANCESCO;RASPANTI, MARIA ELENA;FELETTI, VALENTINA;BUONFIGLIOLI, FEDERICA;CECINATO, PAOLO;MONTAGNANI, MARCO;COLECCHIA, ANTONIO;FESTI, DAVIDE;RODA, ENRICO;MAZZELLA, GIUSEPPE
2009
Abstract
In Intrahepatic Cholestasis of Pregnancy (ICP) an accumulation of bile acids (BA) in the fetal compartment occurs. It is known that a BA efflux is induced by UDCA administration but the molecular basis of this transplacental transport is only partially defined. Aim of the present study was to determine if placental BCRP, able to transport BA, is regulated by UDCA in ICP. Methods: 14 pregnant women with ICP (6 untreated, 37.5±1.33 years; 8 treated with UDCA − 25 mg/kg/day, 32.14±2.16 years) and 7 agematched healthy controls (34.2±1.2 years) have agreed to participate to the study (none had gallstone disease, abnormal liver tests, liver steatosis on ultrasonography). Placentas were obtained at delivery and processed for membrane extraction. Protein expression was evaluated by standard immunoblotting techniques using actin as an internal control. Statistical differences between groups were evaluated by one way ANOVA with Dunn’s Multiple Comparison test. Results: BCRP was expressed only on the apical membrane of the syncytiotrophoblast. A significant difference was observed between the three groups (ANOVA, p = 0.01). BCRP expression was similar in cont rols and in the untreated ICP group. The administration of UDCA induced a significant increase in placental BCRP expression compared to controls (254.5±58.46 vs 100±8.002% of control, p<0.05). Conclusion: In this preliminary study we are able to confirm that BCRP is expressed only on the apical membrane of the syncytiotrophoblast. ICP treatment with high dose UDCA significantly up-regulates placental BCRP expression favouring BA transport towards the foetal compartment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
