Journal: Journal of Molecular Medicine

Abbreviation

J. Mol. Med.

Publisher

Springer

Journal Volumes

ISSN

0946-2716
1432-1440

Description

Filters

2009 - 200922010 - 20193
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Publications 1 - 5 of 5
  • Identification of novel scaffolds targeting Mycobacterium tuberculosis
    Item type: Journal Article
    Dal Molin, Michael; Selchow, Petra; Schäfle, Daniel; et al. (2019)
    Journal of Molecular Medicine
  • Growth hormone replacement therapy regulates microRNA-29a and targets involved in insulin resistance
    Item type: Journal Article
    Galimov, Artur; Hartung, Angelika; Trepp, Roman; et al. (2015)
    Journal of Molecular Medicine
    Replacement of growth hormone (GH) in patients suffering from GH deficiency (GHD) offers clinical benefits on body composition, exercise capacity, and skeletal integrity. However, GH replacement therapy (GHRT) is also associated with insulin resistance, but the mechanisms are incompletely understood. We demonstrate that in GH-deficient mice (growth hormone-releasing hormone receptor (Ghrhr)lit/lit), insulin resistance after GHRT involves the upregulation of the extracellular matrix (ECM) and the downregulation of microRNA miR-29a in skeletal muscle. Based on RNA deep sequencing of skeletal muscle from GH-treated Ghrhrlit/lit mice, we identified several upregulated genes as predicted miR-29a targets that are negative regulators of insulin signaling or profibrotic/proinflammatory components of the ECM. Using gain- and loss-of-function studies, five of these genes were confirmed as endogenous targets of miR-29a in human myotubes (PTEN, COL3A1, FSTL1, SERPINH1, SPARC). In addition, in human myotubes, IGF1, but not GH, downregulated miR-29a expression and upregulated COL3A1. These results were confirmed in a group of GH-deficient patients after 4 months of GHRT. Serum IGF1 increased, skeletal muscle miR-29a decreased, and miR-29a targets were upregulated in patients with a reduced insulin response (homeostatic model assessment of insulin resistance (HOMA-IR)) after GHRT. We conclude that miR-29a could contribute to the metabolic response of muscle tissue to GHRT by regulating ECM components and PTEN. miR-29a and its targets might be valuable biomarkers for muscle metabolism following GH replacement.
  • Subtype-selective GABAA receptor mimetics
    Item type: Review Article
    Zeilhofer, Hanns U.; Witschi, Robert; Hösl, Katharina (2009)
    Journal of Molecular Medicine
  • miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development
    Item type: Journal Article
    Latreille, Mathieu; Herrmanns, Karolin; Renwick, Neil; et al. (2015)
    Journal of Molecular Medicine
    MicroRNAs play a crucial role in the regulation of cell growth and differentiation. Mice with genetic deletion of miR-375 exhibit impaired glycemic control due to decreased β-cell and increased α-cell mass and function. The relative importance of these processes for the overall phenotype of miR-375KO mice is unknown. Here, we show that mice overexpressing miR-375 exhibit normal β-cell mass and function. Selective re-expression of miR-375 in β-cells of miR-375KO mice normalizes both, α- and β-cell phenotypes as well as glucose metabolism. Using this model, we also analyzed the contribution of β-cells to the total plasma miR-375 levels. Only a small proportion (≈1 %) of circulating miR-375 originates from β-cells. Furthermore, acute and profound β-cell destruction is sufficient to detect elevations of miR-375 levels in the blood. These findings are supported by higher miR-375 levels in the circulation of type 1 diabetes (T1D) subjects but not mature onset diabetes of the young (MODY) and type 2 diabetes (T2D) patients. Together, our data support an essential role for miR-375 in the maintenance of β-cell mass and provide in vivo evidence for release of miRNAs from pancreatic β-cells. The small contribution of β-cells to total plasma miR-375 levels make this miRNA an unlikely biomarker for β-cell function but suggests a utility for the detection of acute β-cell death for autoimmune diabetes.
  • Endothelial oxygen sensors regulate tumor vessel abnormalization by instructing phalanx endothelial cells
    Item type: Review Article
    De Bock, Katrien; De Smet, Frederik; Leite De Oliveira, Rodrigo; et al. (2009)
    Journal of Molecular Medicine
Publications 1 - 5 of 5