INVESTIGATING DYNAMICS OF BILE CANALICULI UNDER PHYSIOLOGICAL CONDITIONS AND OBSTRUCTIVE CHOLESTASIS

Abstract

Bile canaliculi (BC) expand and contract periodically to propel bile, however, the mechanism of BC dynamics is not known. Here I have reported the role of intra canalicular pressure (ICP) in regulating BC dynamics via locally regulating biochemical signaling via Ca2+ sensing through Piezo-1 which in turn regulate pericanalicular actomyosin cortex (PAC) activity. Additionally, as a homeostatic response to increased ICP, PAC breaks locally leading to the formation of local membrane protrusion. Under physiological conditions, PAC can repair these protrusions to give rise to inward blebs (IB) like structures. However, beyond a certain threshold ICP (or in obstructive cholestasis), IB bud off the BC membrane as BC derived vesicles (BCV). BCV is a mechanism of bile regurgitation to manage the increased pressure in obstructive cholestasis.

This work has added new insights into the mechanism of BC dynamics and provides a novel mechanism of bile regurgitation which can have therapeutical applications.