8 research outputs found
Sportaktivität und klinisches Outcome nach dreifach Beckenosteotomie nach Tönnis bei angeborener Hüftdysplasie
Long-term Intravascular Blood-Pressure Monitoring with a Novel, Wireless Sensor System - Results from Chronic In-vivo Studies
Sheep models for evaluation of novel patch and prosthesis material in vascular surgery: tips and tricks to avoid possible pitfalls
TCT-105 Long-term Intravascular Blood-Pressure Monitoring with a Novel, Wireless Sensor System – Results from Chronic In-vivo Studies
Superselective Particle Embolization Enhances Efficacy of Radiofrequency Ablation: Effects of Particle Size and Sequence of Action
Lack of Cyclin E1 in hepatocytes aggravates ethanol-induced liver injury and hepatic steatosis in experimental murine model of acute and chronic alcohol-associated liver disease
Background: Cyclin E1 is the regulatory subunit of cyclin-dependent kinase 2 (Cdk2) and one of the central players in cell cycle progression. We recently showed its crucial role for initiation of liver fibrosis and hepatocarcinogenesis. In the present study, we investigated the role of Cyclin E1 in the development of alcohol-associated liver disease (ALD).
Methods: Mice with constitutive (E1-/-), hepatocyte-specific (Cyclin E1Δhepa), or intestinal-epithelial-cell-specific (Cyclin E1ΔIEC) inactivation of Cyclin E1 and corresponding wild type littermate controls (WT) were administered either a Lieber-DeCarli ethanol diet (LDE) for 3 weeks or acute ethanol binges (6 g/kg) through oral gavage. Serum parameters of liver functionality were measured; hepatic tissues were collected for biochemical and histological analyses.
Results: The administration of acute EtOH binge and chronic LDE diet to E1-/- mice enhanced hepatic steatosis, worsened liver damage and triggered body weight loss. Similarly, in the acute EtOH binge model, Cyclin E1Δhepa mice revealed a significantly worsened liver phenotype. In contrast, inactivation of Cyclin E1 only in intestinal epithelial cell (IECs)did not lead to any significant changes in comparison to WT mice after acute EtOH challenge. Remarkably, both acute and chronic EtOH administration in E1-/- animals resulted in increased levels of ADH and decreased expression of ALDH1/2. The additional application of a pan-Cdk inhibitor (S-CR8) further promoted liver damage in EtOH-treated WT mice.
Conclusion: Our data point to a novel unexpected role of Cyclin E1 in hepatocytes for alcohol metabolism, which seems to be independent of the canonical Cyclin E1/Cdk2 function as a cell cycle regulator.Fundación Alemana de Investigación (DFG)Ministerio de Asuntos Económicos y Transformación Digital (MINECO)Ministerio de Ciencia e Innovación (MICIN)Unión EuropeaComunidad de Madrid. Fundación para la Investigación Biomédica del Hospital Universitario de Getafe (FIBHGM)European Cooperation in Science & Technology (COST)Universidad Complutense de Madrid /Banco SantanderDepto. de Genética, Fisiología y MicrobiologíaDepto. de Inmunología, Oftalmología y ORLFac. de Ciencias BiológicasFac. de MedicinaTRUEpu