About this Research Topic
Cholestasis – the disruption of bile flux, is a symptom of all liver pathologies, leading to accumulation of toxic bile constituents in the liver tissue and exacerbating liver injury. As liver diseases are now part of the top three afflictions challenging Western societies, there is renewed interest in understanding cholestasis in the hopes of developing clinical interventions. Yet, the mechanisms by which cholestasis is initiated and its precise implications are poorly understood. The last decade has seen advances in our knowledge of cholestatic liver diseases – from the development of imaging techniques that can probe liver tissue with sub-cellular resolution and molecular specificity, to the development of transgenic mouse models that recapitulate cholestasis.
The field of cholestasis research is currently in phase of resurgence and fundamental aspects of liver function and physiology are being re-evaluated. These advances have revealed cholestatic pathology to be an intricate phenomenon arising out of the interplay of various liver cell populations (hepatocytes, cholangiocytes, immune cells, stellate cells), metabolism, transcription changes and cellular signal transduction.
We have learnt that the liver has conserved adaptive mechanisms to deal with cholestasis that involves alternation of molecular transporters in the short term, followed by tissue remodeling by cholangiocytes. Mechanisms of bile toxicity are now understood as an outcome of bile acids as signaling molecules, rather than due to the simplified ‘hydrophobic detergent’ hypothesis. Biliary flux has now been directly observed at sub-cellular resolution. The decades old assumption of bile acids driving osmotic water influx to create bile flow in canalicular and ductular microdomains has been corrected. Instead, the canalicular network seems to be a specialized glandular acinus through which bile acids merely diffuse along a concentration gradient. These studies have implications on the development of choleretic (anti-cholestatic) drugs. Multiple lines of evidence – molecular, pharmacological, and physiological now show that the clinical choleretic agents such as UDCA likely also act through the alteration of bile acid metabolism and signaling, rather than simple ‘super-osmolytes’ as previously imagined.
The goal of this Research Topic is to integrate these divergent studies into a modern understanding of the liver and to develop concepts for translation into therapies for the clinic.
We welcome Original Research and Review articles. Areas to be covered may include, but are not limited to:
• Cholangiocyte biology
• Hepatocyte biology – transporters, metabolism, signal transduction
• Intravital imaging of the liver
• Cholangiopathies – PSC, PBC, Chonagiocarcinoma
• Bile - constituents, modifications, bile circulation: cholehepatic, enterohepatic
• Clinical treatment - choleretics
• Physiology of the bile duct, gall bladder
• Adaptive mechanisms in the liver in response to pathology
Topic Editor Peter Jansen is part of safety monitoring committees of clinical trials for liver pathologies. The other Topic Editors declare no competing conflicts of interest related to the theme of the Research Topic
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