title: Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids.
abstract: Flavonoids were found previously to modulate efficiency of synthesis of glycosaminoglycans (GAGs), compounds which are accumulated in cells of patients suffering from mucopolysaccharidoses (MPSs). The aim of this work was to determine effects of different flavonoids (genistein, kaempferol, daidzein) used alone or in combinations, on expression of genes coding for proteins involved in GAG metabolism. Analyses with DNA microarray, followed by real-time qRT-PCR revealed that genistein, kaempferol and combination of these two compounds induced dose- and time-dependent remarkable alterations in transcript profiles of GAG metabolism genes in cultures of wild-type human dermal fibroblasts (HDFa). Interestingly, effects of the mixture of genistein and kaempferol were stronger than those revealed by any of these compounds used alone. Similarly, the most effective reduction in levels of GAG production, in both HDFa and MPS II cells, was observed in the presence of genistein, keampferol and combination of these compounds. Forty five genes were chosen for further verification not only in HDFa, but also in MPS II fibroblasts by using real-time qRT-PCR. Despite effects on GAG metabolism-related genes, we found that genistein, kaempferol and mixture of these compounds significantly stimulated expression of TFEB. Additionally, a decrease in MTOR transcript level was observed at these conditions.
authors: Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors: Marta
authors: M
authors: Moskot
authors: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors: Joanna
authors: J
authors: Jakóbkiewicz-Banecka
authors: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors: Anna
authors: A
authors: Kloska
authors: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors: Elwira
authors: E
authors: Smolińska
authors: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors: Paweł
authors: P
authors: Mozolewski
authors: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors: Marcelina
authors: M
authors: Malinowska
authors: Department of Molecular Virology, Intercollegiate Faculty of Biotechnology UG-MUG, Kładki 24, 80-822 Gdańsk, Poland.
authors: Michał
authors: M
authors: Rychłowski
authors: Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology UG-MUG, Kładki 24, 80-822 Gdańsk, Poland.
authors: Bogdan
authors: B
authors: Banecki
authors: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors: Grzegorz
authors: G
authors: Węgrzyn
authors: Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308 Gdańsk, Poland.
authors: Magdalena
authors: M
authors: Gabig-Cimińska
mesh_terms: D016022:Case-Control Studies; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D019833:Genistein / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D044949:Kaempferols / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000235:genetics; D046228:Microarray Analysis; D058977:Molecular Sequence Annotation; D016532:Mucopolysaccharidosis II / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D061251:Primary Cell Culture
chemical_list: D006025:Glycosaminoglycans; D007529:Isoflavones; D044949:Kaempferols; C004742:daidzein; C006552:kaempferol; D019833:Genistein