Publications by authors named "R C Huebert"
LncRNAs, RNA Therapeutics, and Emerging Technologies in Liver Pathobiology.
Semin Liver Dis
December 2024
Article Synopsis
- The review focuses on long noncoding RNAs (lncRNAs) and their critical roles in various liver diseases, including fatty liver disease, liver cancer, and other cholangiopathies.
- It discusses how specific lncRNAs influence processes like lipid metabolism, inflammation, and cancer development, showcasing their potential as diagnostic tools and therapeutic targets.
- Advancements in RNA-based therapies and technologies are paving the way for personalized medicine, highlighting the importance of continued research into lncRNAs for better understanding and treatment of liver diseases.
Background: Fibroinflammatory cholangiopathies, such as primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), are characterized by inflammation and biliary fibrosis, driving disease-related complications. In biliary fibrosis, cholangiocytes activated by transforming growth factor-β (TGFβ) release signals that recruit immune cells to drive inflammation and activate hepatic myofibroblasts to deposit the extracellular matrix (ECM). TGFβ regulates stearoyl-CoA desaturase (SCD), an enzyme that catalyzes the synthesis of monounsaturated fatty acids, in stimulating fibroinflammatory lipid signaling.
View Article and Find Full Text PDFCholangiopathies comprise a spectrum of chronic intrahepatic and extrahepatic biliary tract disorders culminating in progressive cholestatic liver injury, fibrosis, and often cirrhosis and its sequela. Treatment for these diseases is limited, and collectively, they are one of the therapeutic "black boxes" in clinical hepatology. The etiopathogenesis of the cholangiopathies likely includes disease-specific mediators but also common cellular and molecular events driving disease progression (eg, cholestatic fibrogenesis, inflammation, and duct damage).
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- Liver fibrosis involves the activation of hepatic stellate cells (HSCs) and the release of extracellular vesicles (EVs), with increased glycolysis in HSCs playing a key role in this process.
- Genetic inhibition of glycolysis in HSCs was shown to reduce liver fibrosis and alter the expression of EV-related pathways specifically in the liver's pericentral zone.
- The study suggests that targeting glycolysis in HSCs could serve as a new therapeutic approach to mitigate liver fibrosis by decreasing the release of fibrogenic EVs.
In this study, a mixed porcine-human bioengineered liver (MPH-BEL) was used in a preclinical setup of extracorporeal liver support devices as a treatment for a model of post-resection liver failure (PRLF). The potential for human clinical application is further illustrated by comparing the functional capacity of MPH-BEL grafts as assessed using this porcine PRLF model with fully human (FH-BEL) grafts which were perfused and assessed in vitro. BEL grafts were produced by reseeding liver scaffolds with HUVEC and primary porcine hepatocytes (MPH-BEL) or primary human hepatocytes (FH-BEL).
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