| Autor: |
Tsitrina AA; Koltzov Institute of Developmental Biology, 26 Vavilov Str., 119334 Moscow, Russia.; Ilse Katz Institute for Nanoscale Science & Technology, Ben-Gurion University of the Negev, Beer-Sheva P.O. Box 653, Israel., Halimani N; V. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, 143025 Moscow, Russia., Andreichenko IN; V. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, 143025 Moscow, Russia., Sabirov M; Koltzov Institute of Developmental Biology, 26 Vavilov Str., 119334 Moscow, Russia., Nesterchuk M; V. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, 143025 Moscow, Russia., Dashenkova NO; Koltzov Institute of Developmental Biology, 26 Vavilov Str., 119334 Moscow, Russia., Romanov R; Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria., Bulgakova EV; Koltzov Institute of Developmental Biology, 26 Vavilov Str., 119334 Moscow, Russia., Mikaelyan A; Koltzov Institute of Developmental Biology, 26 Vavilov Str., 119334 Moscow, Russia., Kotelevtsev Y; V. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, 143025 Moscow, Russia. |
| Abstrakt: |
4-methylumbelliferone (4MU) is a well-known hyaluronic acid synthesis inhibitor and an approved drug for the treatment of cholestasis. In animal models, 4MU decreases inflammation, reduces fibrosis, and lowers body weight, serum cholesterol, and insulin resistance. It also inhibits tumor progression and metastasis. The broad spectrum of effects suggests multiple and yet unknown targets of 4MU. Aiming at 4MU target deconvolution, we have analyzed publicly available data bases, including: 1. Small molecule library Bio Assay screening (PubChemBioAssay); 2. GO pathway databases screening; 3. Protein Atlas Database. We also performed comparative liver transcriptome analysis of mice on normal diet and mice fed with 4MU for two weeks. Potential targets of 4MU public data base analysis fall into two big groups, enzymes and transcription factors (TFs), including 13 members of the nuclear receptor superfamily regulating lipid and carbohydrate metabolism. Transcriptome analysis revealed changes in the expression of genes involved in bile acid metabolism, gluconeogenesis, and immune response. It was found that 4MU feeding decreased the accumulation of the glycogen granules in the liver. Thus, 4MU has multiple targets and can regulate cell metabolism by modulating signaling via nuclear receptors. |
