Cellular and Gene Expression Response to the Combination of Genistein and Kaempferol in the Treatment of Mucopolysaccharidosis Type I

Węsierska, Magdalena; Kloska, Anna; Medina, Diego L.; Jakóbkiewicz-Banecka, Joanna; Gabig-Cimińska, Magdalena; Radzińska, Marta; Moskot, Marta; Malinowska, Marcelina

doi:10.3390/ijms23031058

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Cellular and Gene Expression Response to the Combination of Genistein and Kaempferol in the Treatment of Mucopolysaccharidosis Type I

Magdalena Węsierska

Anna Kloska

Diego L. Medina

^2,3

Joanna Jakóbkiewicz-Banecka

¹,

Magdalena Gabig-Cimińska

^1,4

Marta Radzińska

¹,

Marta Moskot

^1,4,* and

Marcelina Malinowska

^1,*

Department of Medical Biology and Genetics, Faculty of Biology University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland

Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Naples, Italy

Medical Genetics Unit, Department of Medical and Translational Science, Federico II University, Via Pansini 5, 80131 Naples, Italy

⁴

Laboratory of Molecular Biology of Human Skin Diseases, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Kładki 24, 80-822 Gdańsk, Poland

Authors to whom correspondence should be addressed.

Academic Editor: Cristobal Miranda

Int. J. Mol. Sci. 2022, 23(3), 1058; https://doi.org/10.3390/ijms23031058

Received: 16 December 2021 / Revised: 8 January 2022 / Accepted: 11 January 2022 / Published: 19 January 2022

(This article belongs to the Special Issue Animal and Plant Cell–Tissue, Organ Specialization and Function: Investigational, Experimental and Medical Aspects 2.0)

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Abstract

Flavonoids are investigated as therapeutics for mucopolysaccharidosis, a metabolic disorder with impaired glycosaminoglycan degradation. Here we determined the effects of genistein and kaempferol, used alone or in combination, on cellular response and gene expression in a mucopolysaccharidosis type I model. We assessed the cell cycle, viability, proliferation, subcellular localization of the translocation factor EB (TFEB), number and distribution of lysosomes, and glycosaminoglycan synthesis after exposure to flavonoids. Global gene expression was analysed using DNA microarray and quantitative PCR. The type and degree of flavonoid interaction were determined based on the combination and dose reduction indexes. The combination of both flavonoids synergistically inhibits glycosaminoglycan synthesis, modulates TFEB localization, lysosomal number, and distribution. Genistein and kaempferol in a 1:1 ratio regulate the expression of 52% of glycosaminoglycan metabolism genes. Flavonoids show synergy, additivity, or slight antagonism in all analysed parameters, and the type of interaction depends on the concentration and component ratios. With the simultaneous use of genistein and kaempferol in a ratio of 4:1, even a 10-fold reduction in the concentration of kaempferol is possible. Flavonoid mixtures, used as the treatment of mucopolysaccharidosis, are effective in reducing glycosaminoglycan production and storage and show a slight cytotoxic effect compared to single-flavonoid usage. View Full-Text

Keywords: flavonoids; GAG metabolism; gene expression; mucopolysaccharidosis type I

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Węsierska, M.; Kloska, A.; Medina, D.L.; Jakóbkiewicz-Banecka, J.; Gabig-Cimińska, M.; Radzińska, M.; Moskot, M.; Malinowska, M. Cellular and Gene Expression Response to the Combination of Genistein and Kaempferol in the Treatment of Mucopolysaccharidosis Type I. Int. J. Mol. Sci. 2022, 23, 1058. https://doi.org/10.3390/ijms23031058

AMA Style

Węsierska M, Kloska A, Medina DL, Jakóbkiewicz-Banecka J, Gabig-Cimińska M, Radzińska M, Moskot M, Malinowska M. Cellular and Gene Expression Response to the Combination of Genistein and Kaempferol in the Treatment of Mucopolysaccharidosis Type I. International Journal of Molecular Sciences. 2022; 23(3):1058. https://doi.org/10.3390/ijms23031058

Chicago/Turabian Style

Węsierska, Magdalena, Anna Kloska, Diego L. Medina, Joanna Jakóbkiewicz-Banecka, Magdalena Gabig-Cimińska, Marta Radzińska, Marta Moskot, and Marcelina Malinowska. 2022. "Cellular and Gene Expression Response to the Combination of Genistein and Kaempferol in the Treatment of Mucopolysaccharidosis Type I" International Journal of Molecular Sciences 23, no. 3: 1058. https://doi.org/10.3390/ijms23031058

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Cellular and Gene Expression Response to the Combination of Genistein and Kaempferol in the Treatment of Mucopolysaccharidosis Type I

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