Showing papers by "Julie Venter published in 2013"
TL;DR: Overexpression of AANAT in cholangiocyte cell lines decreased the basal proliferative rate and expression of SR, CFTR, and Cl−/HCO 3− AE2 and ablated secretin‐stimulated biliary secretion in these cells.
41 citations
TL;DR: The differentiation of small into large cholangiocytes may be important in the replenishment of the biliary epithelium during damage of large, senescent cholangsiocytes.
35 citations
TL;DR: This paper is a review of the literature regarding melatonin in the gastrointestinal tract and as a potential therapy for gastrointestinal cancers.
Abstract: Melatonin exerts a multitude of physiological functions including the regulation of the sleep cycle and circadian rhythm. Although the synthesis of melatonin in the pineal gland is regulated by changes in the light/dark cycle, the release of melatonin in the gastrointestinal tract is related to food consumption. Melatonin regulates antioxidative processes and it improves T-helper cell response by stimulating the production of specific cytokines. Melatonin is directly involved in preventing tumor initiation, promotion, and progression in a variety of cancers of the gastrointestinal tract including colorectal cancer, cholangiocarcinoma, hepatocarcinoma, and pancreatic carcinoma. This paper is a review of the literature regarding melatonin in the gastrointestinal tract and as a potential therapy for gastrointestinal cancers.
15 citations
TL;DR: Therapies targeting NPY-mediated signaling may prove beneficial for the treatment of cholangiopathies and the paracrine/autocrine effects of NPY on cholangsiocyte proliferation are determined.
Abstract: Neuropeptide Y (NPY) exerts its functions through six subtypes of receptors (Y1–Y6). Biliary homeostasis is regulated by several factors through autocrine/paracrine signaling. NPY inhibits cholangi...
9 citations
TL;DR: The study introduces the novel concept that cholangiocytes express and secrete secretin and that manipulation of this gene may be an important target for the management of biliary disorders.
Abstract: Background: Secretin stimulates bicarbonate secretion in large ducts by interaction with receptors by a cAMP-dependent pathway [1]. In BDL rats, the growth of large (but not small) cholangiocytes is activated by the cAMP/ERK1/2/Elk-1 pathway; and is associated with increased secretin receptor (SR) expression [2]. The aim of our study was to define the role of secretin in experimental models of cholestatic mice. Methods: We used (SEC+/+) (wild-type, WT) and SEC-/- male mice that underwent sham surgery or BDL for 7 days treated with saline or secretin. Then, we used: (i) liver sections to evaluate secretin protein expression, cholangiocyte growth, apoptosis, the presence of VEGF-A/C and NGF; (ii) purified and immortalized small and large BDL cholangiocytes to measure PCNA protein expression and the same previous growth factors. Results: In vivo, we demonstrated that: (i) secretin is expressed in normal liver by large bile ducts; and (ii) secretin expression increases in large bile ducts following BDL. Isolated large cholangiocytes from BDL WT mice express higher levels of the mRNA for secretin and secrete greater amounts of this hormone compared to normal large cholangiocytes. Knockout of the secretin gene reduced BDL-induced increase in large IBDM compared to WT BDL mice, an event that was associated with enhanced apoptosis of large cholangiocytes and decreased expression of VEGF-A/C and NGF. Concomitant with reduced large IBDM there was increased small IBDM in SEC-/- KO BDL mice compared to WT BDL mice. After prolonged treatment, secretin increased the biliary expression of PCNA, VEGF-A/C and NGF. Conclusions: The study introduces the novel concept that cholangiocytes express and secrete secretin and that manipulation of this gene may be an important target for the management of biliary disorders.