Author response: MicroRNA-26b protects against MASH development in mice and can be efficiently targeted with lipid nanoparticles
Abstract
Fatty liver disease is a condition characterized by the abnormal accumulation of fat in the liver. In certain cases, the fatty build-up can lead to inflammation and, in time, scarring. This advanced stage is known as MASH (short for metabolic dysfunction-associated steatohepatitis), and it can increase the risk of liver failure, cancer, and other complications. Yet the underlying mechanisms that initiate inflammation and thereby drive the disease are still poorly understood. Identifying the molecular factors contributing to this transition could aid in discovering new treatment targets. To explore this question, Peters et al. focus on microRNA-26b, a small molecule involved in many heart and metabolic diseases that helps regulate gene expression. They aimed to clarify the role of microRNA-26b in MASH using mice genetically manipulated to lack this regulatory molecule. The experiments revealed that the animals had larger amounts of fat in their livers, with the organs also showing clear signs of scarring and increased inflammation – including high levels of inflammatory signalling molecules and the presence of immune cells known as macrophages. Peters et al. then treated the animals with specially designed compounds that can act as microRNA-26b. The molecules were safely delivered to the liver within tiny fat-based spheres known as lipid nanoparticles. Following such treatment, the mice showed decreased levels of liver fat and inflammation. The anti-inflammatory effect of the microRNA-26b ‘mimics’ was also confirmed in human liver samples. Together, these results show that microRNA-26b plays a protective role in the development of MASH. Future research should focus on confirming whether these molecules could represent a viable therapeutic treatment, in particular when delivered within lipid-based nanoparticles.
Authors 24
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Linsey J. F. Peters Aachen
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RWTH Aachen University
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Leonida Rakateli Aachen
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RWTH Aachen University
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Rosanna Huchzermeier Aachen
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RWTH Aachen University
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Andrea Bonnin-Marquez Aachen
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RWTH Aachen University
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Sanne Lidewij Maas Aachen
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RWTH Aachen University
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Cheng Lin Aachen
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RWTH Aachen University
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Alexander Jans Aachen
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RWTH Aachen University
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University of Groningen
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University of Groningen
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Maastricht University
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Maastricht University
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University of Groningen
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Medical University Vienna
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Saarland University
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Saarland University
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Joachim Jankowski Aachen
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RWTH Aachen University
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Ludwig-Maximilians-Universität München
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Ludwig-Maximilians-Universität München
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Ludwig-Maximilians-Universität München
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Ludwig Maximilian University of Munich
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Maastricht University Medical Centre
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Maastricht University Medical Centre
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Affiliation as printed
Maastricht University
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Maastricht University Medical Centre
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Maastricht University Medical Centre
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University of Bern
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Matthias Bartneck Aachen
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RWTH Aachen University
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Emiel P. C. van der Vorst Aachen
Affiliation as printed
RWTH Aachen University
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