Gianfranco Alpini, PhD and his lab have made significant contributions to the understanding of the factors that influence the rate of proliferation of cholangiocytes. Specifically, the group demonstrated the importance of: (i) adrenergic, cholinergic, dopaminergic and serotoninergic fibers and receptors; and (ii) sensory nerves (Calcitonin Gene-Related Peptide and substance P) and their receptors in the regulation of biliary growth/damage.
Most recently, the Alpini Lab has found that cholangiocytes (in addition to the pineal gland) express the enzyme arylalkylamine N-acetyltransferase (AANAT), necessary for melatonin synthesis, and secrete melatonin locally. This recent study demonstrates that cholangiocyte proliferation is regulated by both paracrine (melatonin secreted by the pineal gland) and autocrine (melatonin secreted locally by cholangiocytes) pathways through the modulation of the circadian rhythm and the synthesis of clock genes, which a number of studies have shown to be important in a number of gastrointestinal disorders. It has also introduced the novel concept of the interaction between the brain and cholangiocytes (liver-brain axis) in the regulation of biliary proliferation and secretory function.
