1.Cellular crosstalk during cholestatic liver injury
Thomson JOANNE ; Hargrove LAURA ; Kennedy LINDSEY ; Demieville JENNIFER ; Francis HEATHER
Liver Research 2017;1(1):26-33
The functions of the liver are very diverse.From detoxifying blood to storing glucose in the form of glycogen and producing bile to facilitate fat digestion,the liver is a very active and important organ.The liver is comprised of many varied cell types whose functions are equally diverse.Cholangiocytes line the biliary tree and aid in transporting and adjusting the composition of bile as it travels to the gallbladder.Hepatic stellate cells and portal fibroblasts are located in different areas within the liver architecture,but both contribute to the development of fibrosis upon activation after liver injury.Vascular cells,including those that constitute the peribiliary vascular plexus,are involved in functions other than blood delivery to and from the liver,such as supporting the growth of the biliary tree during development.Mast cells are normally found in healthy livers but in very low numbers.However,after injury,mast cell numbers greatly increase as they infiltrate and release factors that exacerbate the fibrotic response.While not an all-inclusive list,these cells have individual roles within the liver,but they are also able to communicate with each other by cellular crosstalk.In this review,we examine some of these pathways that can lead to an increase in the homeostatic dysfunction seen in liver injury.
2.Diagnostic and therapeutic potentials of microRNAs in cholangiopathies
Kennedy LINDSEY ; Francis HEATHER ; Meng FANYIN ; Glaser SHANNON ; Alpini GIANFRANCO
Liver Research 2017;1(1):34-41
Cholangiopathies are a group of rare,devastating diseases that arise from damaged cholangiocytes,the cells that line the intra-and extra-hepatic bile ducts of the biliary epithelium.Cholangiopathies result in significant morbidity and mortality and are a major cause of liver transplantation.A better understanding of the underlying pathogenesis that influences cholangiocyte dysregulation and cholangiopathy pro-gression is necessary,considering the dismal prognosis associated with these diseases. MicroRNAs are a class of small,non-coding RNAs that regulate post-transcriptional mRNA expression of specific genes.The role of microRNAs has expanded to include the initiation and development of many diseases,including cholangiopathies.Understanding microRNA regulation of cholangiopathies may provide diagnostic and therapeutic benefit for these diseases.In this review,the authors primarily focus on studies published within the last five years that help determine the diagnostic and therapeutic po-tential of microRNAs in cholangiopathies.
3.Alcoholic liver disease and mast cells:What's your gut got to do with it?
Tolefree Ann JULIE ; Garcia Joy ABIGAIL ; Farrell JENEE ; Meadows VIK ; Kennedy LINDSEY ; Hargrove LAURA ; Demieville JENNIFER ; Francis NICOLE ; Mirabel JULIA ; Francis HEATHER
Liver Research 2019;3(1):46-54
Alcoholic liver disease(ALD)remains one of the leading causes of liver injury and death when left un-treated.The gut microbiota has been recognized as a key regulator of a number of pathologies,including ALD.The role of mast cells(MCs)during liver disease progression has been demonstrated in a number of animal models and in human liver diseases.The interaction between the gut microbiota and MCs has been investigated,and links between the gut and these immune cells are being uncovered.The interplay between the gut microbiota and MCs during ALD has been evaluated and studies suggest that there could be an important link between MCs,their mediators and gut inflammation during the progression of ALD.