Browsing by Subject "Bile duct"

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    Biliary Epithelial Senescence in Liver Disease: There Will Be SASP
    (Frontiers Media, 2021-12-21) Meadows, Vik; Baiocchi, Leonardo; Kundu, Debjyoti; Sato, Keisaku; Fuentes, Yessenia; Wu, Chaodong; Chakraborty, Sanjukta; Glaser, Shannon; Alpini, Gianfranco; Kennedy, Lindsey; Francis, Heather; Medicine, School of Medicine
    Cellular senescence is a pathophysiological phenomenon in which proliferative cells enter cell cycle arrest following DNA damage and other stress signals. Natural, permanent DNA damage can occur after repetitive cell division; however, acute stress or other injuries can push cells into premature senescence and eventually a senescence-associated secretory phenotype (SASP). In recent years, there has been increased evidence for the role of premature senescence in disease progression including diabetes, cardiac diseases, and end-stage liver diseases including cholestasis. Liver size and function change with aging, and presumably with increasing cellular senescence, so it is important to understand the mechanisms by which cellular senescence affects the functional nature of the liver in health and disease. As well, cells in a SASP state secrete a multitude of inflammatory and pro-fibrogenic factors that modulate the microenvironment. Cellular SASP and the associated, secreted factors have been implicated in the progression of liver diseases, such as cholestatic injury that target the biliary epithelial cells (i.e., cholangiocytes) lining the bile ducts. Indeed, cholangiocyte senescence/SASP is proposed to be a driver of disease phenotypes in a variety of liver injuries. Within this review, we will discuss the impact of cholangiocyte senescence and SASP in the pathogenesis of cholestatic disorders.
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    Concise Review: Functional Roles and Therapeutic Potentials of Long Non-coding RNAs in Cholangiopathies
    (Frontiers Media, 2020-02) Sato, Keisaku; Glaser, Shannon; Francis, Heather; Alpini, Gianfranco; Medicine, School of Medicine
    Long non-coding RNAs (lncRNAs) are RNAs with lengths exceeding 200 nucleotides that are not translated into proteins. It is well-known that small non-coding RNAs, such as microRNAs (miRNAs), regulate gene expression and play an important role in cholangiopathies. Recent studies have demonstrated that lncRNAs may also play a key role in the pathophysiology of cholangiopathies. Patients with cholangiopathies often develop cholangiocarcinoma (CCA), which is cholangiocyte-derived cancer, in the later stage. Cholangiocytes are a primary target of therapies for cholangiopathies and CCA development. Previous studies have demonstrated that expression levels of lncRNAs are altered in the liver of cholangiopathies or CCA tissues. Some lncRNAs regulate gene expression by inhibiting functions of miRNAs leading to diseased liver conditions or CCA progression, suggesting that lncRNAs could be a novel therapeutic target for those disorders. This review summarizes current understandings of functional roles of lncRNAs in cholangiopathies and seek their potentials for novel therapies.