Inhibition of the liver expression of arylalkylamine N-acetyltransferase increases the expression of angiogenic factors in cholangiocytes.
OBJECTIVE
Reduction of biliary serotonin N-acetyltransferase (AANAT) expression and melatonin administration/secretion in cholangiocytes increases biliary proliferation and the expression of SR, CFTR and Cl(-)/HCO3 (-) AE2. The balance between biliary proliferation/damage is regulated by several autocrine neuroendocrine factors including vascular endothelial growth factor-A/C (VEGF-A/C). VEGFs are 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 the cholangiocytes synthesis of VEGF-A/C.


RESULTS
The decrease in AANAT expression and subsequent lower melatonin secretion by cholangiocytes was associated with increased expression of VEGF-A/C. Overexpression of AANAT in cholangiocyte lines decreased the expression of VEGF-A/C.


CONCLUSIONS
Modulation of melatonin synthesis may affect the expression of VEGF-A/C by cholangiocytes and may modulate the hepatic microvascularization through the regulation of VEGF-A/C expression regulating biliary functions.
1 Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy ; 2 Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy ; 3 Research, Central Texas Veterans Health Care System, 4 Scott & White Digestive Disease Research Center, Scott & White, Academic Operations, Scott & White, 5 Department of Medicine, Division Gastroenterology, Texas A&M Health Science Center, College of Medicine, Temple, TX 76504, USA.
Anastasia
A
Renzi
1 Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy ; 2 Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy ; 3 Research, Central Texas Veterans Health Care System, 4 Scott & White Digestive Disease Research Center, Scott & White, Academic Operations, Scott & White, 5 Department of Medicine, Division Gastroenterology, Texas A&M Health Science Center, College of Medicine, Temple, TX 76504, USA.
Romina
R
Mancinelli
1 Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy ; 2 Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy ; 3 Research, Central Texas Veterans Health Care System, 4 Scott & White Digestive Disease Research Center, Scott & White, Academic Operations, Scott & White, 5 Department of Medicine, Division Gastroenterology, Texas A&M Health Science Center, College of Medicine, Temple, TX 76504, USA.
Paolo
P
Onori
1 Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy ; 2 Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy ; 3 Research, Central Texas Veterans Health Care System, 4 Scott & White Digestive Disease Research Center, Scott & White, Academic Operations, Scott & White, 5 Department of Medicine, Division Gastroenterology, Texas A&M Health Science Center, College of Medicine, Temple, TX 76504, USA.
Antonio
A
Franchitto
1 Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy ; 2 Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy ; 3 Research, Central Texas Veterans Health Care System, 4 Scott & White Digestive Disease Research Center, Scott & White, Academic Operations, Scott & White, 5 Department of Medicine, Division Gastroenterology, Texas A&M Health Science Center, College of Medicine, Temple, TX 76504, USA.
Gianfranco
G
Alpini
1 Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy ; 2 Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy ; 3 Research, Central Texas Veterans Health Care System, 4 Scott & White Digestive Disease Research Center, Scott & White, Academic Operations, Scott & White, 5 Department of Medicine, Division Gastroenterology, Texas A&M Health Science Center, College of Medicine, Temple, TX 76504, USA.
Shannon
S
Glaser
1 Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza, Rome, Italy ; 2 Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy ; 3 Research, Central Texas Veterans Health Care System, 4 Scott & White Digestive Disease Research Center, Scott & White, Academic Operations, Scott & White, 5 Department of Medicine, Division Gastroenterology, Texas A&M Health Science Center, College of Medicine, Temple, TX 76504, USA.
Eugenio
E
Gaudio
Serotonin N-acetyltransferase (AANAT); biliary proliferation; vascular endothelial growth factor-A/C (VEGF-A/C)