Author/Authors :
renzi, anastasia university of rome - department of anatomical, histological, forensic medicine and orthopedic sciences, Rome, Italy , mancinelli, romina university of rome - department of anatomical, histological, forensic medicine and orthopedic sciences, Rome, italy , onori, paolo university of rome - department of anatomical, histological, forensic medicine and orthopedic sciences, Rome, Italy , franchitto, antonio university of rome - department of anatomical, histological, forensic medicine and orthopedic sciences, Rome, Italy , franchitto, antonio eleonora lorillard spencer cenci foundation, Rome, Italy , alpini, gianfranco texas a m health science center - college of medicine - department of medicine, division gastroenterology, Temple, USA , alpini, gianfranco scott white digestive disease research center, USA , alpini, gianfranco central texas veterans health care system, usa , glaser, shannon central texas veterans health care system, USA , glaser, shannon texas a m health science center - college of medicine - department of medicine, division gastroenterology, Temple, USA , glaser, shannon scott white digestive disease research center, USA , gaudio, eugenio university of rome - department of anatomical, histological, forensic medicine and orthopedics sciences, Rome, Italy
Abstract :
Background and aims: Reduction of biliary serotonin N-acetyltransferase (AANAT) expression andmelatonin administration/secretion in cholangiocytes increases biliary proliferation and the expression ofSR, CFTR and Cl–/HCO3– AE2. The balance between biliary proliferation/damage is regulated by severalautocrine neuroendocrine factors including vascular endothelial growth factor-A/C (VEGF-A/C). VEGFsare secreted by several epithelia, where they modulate cell growth by autocrine and paracrine mechanisms.No data exists regarding the effect of AANAT modulation on the expressions of VEGFs by cholangiocytes.Methods: In this study, we evaluated the effect of local modulation of biliary AANAT expression on thecholangiocytes synthesis of VEGF-A/C.Results: The decrease in AANAT expression and subsequent lower melatonin secretion by cholangiocyteswas associated with increased expression of VEGF-A/C. Overexpression of AANAT in cholangiocyte linesdecreased the expression of VEGF-A/C.Conclusions: Modulation of melatonin synthesis may affect the expression of VEGF-A/C bycholangiocytes and may modulate the hepatic microvascularization through the regulation of VEGF-A/Cexpression regulating biliary functions.
Keywords :
Serotonin N , acetyltransferase (AANAT) , vascular endothelial growth factor , A , C (VEGF , A , C) , biliaryproliferation
