{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:44:57Z","timestamp":1792691097055,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Mucopolysaccharidoses (MPS) are inherited metabolic disorders caused by mutations leading to dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs). Due to their impaired degradation, GAGs accumulate in cells of patients, which results in dysfunction of tissues and organs. Substrate reduction therapy is one of potential treatment of these diseases. It was demonstrated previously that genistein (4', 5, 7-trihydroxyisoflavone) inhibits synthesis and reduces levels of GAGs in cultures of fibroblasts of MPS patients. Recent pilot clinical study indicated that such a therapy may be effective in MPS III (Sanfilippo syndrome).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>To learn on details of the molecular mechanism of genistein-mediated inhibition of GAG synthesis, efficiency of this process was studied by measuring of incorporation of labeled sulfate, storage of GAGs in lysosomes was estimated by using electron microscopic techniques, and efficiency of phosphorylation of epidermal growth factor (EGF) receptor was determined by using an ELISA-based assay with fluorogenic substrates.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Effects of genistein on inhibition of GAG synthesis and accumulation in fibroblasts from patients suffering from various MPS types were abolished in the presence of an excess of EGF, and were partially reversed by an increased concentration of genistein. No such effects were observed when an excess of 17\u03b2-estradiol was used instead of EGF. Moreover, EGF-mediated stimulation of phsophorylation of the EGF receptor was impaired in the presence of genistein in both wild-type and MPS fibroblasts.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The results presented in this report indicate that the mechanism of genistein-mediated inhibition of GAG synthesis operates through epidermal growth factor (EGF)-dependent pathway.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1423-0127-16-26","type":"journal-article","created":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T19:17:50Z","timestamp":1243538270000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway"],"prefix":"10.1186","volume":"16","author":[{"given":"Joanna","family":"Jak\u00f3bkiewicz-Banecka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Piotrowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Narajczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Bara\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"W\u0119grzyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,3,2]]},"reference":[{"key":"26_CR1","first-page":"3421","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"EF Neufeld","year":"2001","unstructured":"Neufeld EF, Muenzer J: The mucopolysaccharidoses. The Metabolic and Molecular Bases of Inherited Disease. Edited by: Scriver CR, Beaudet AL, Valle D, Sly WS. 2001, New York: McGraw-Hill Co, 3: 3421-3452. 8","edition":"8"},{"key":"26_CR2","first-page":"13","volume-title":"Genetic Metabolic Disorders: Management, Costs and Sociomedical Aspects","author":"M Beck","year":"2007","unstructured":"Beck M: Mucopolysaccharidoses: clinical features and management. Genetic Metabolic Disorders: Management, Costs and Sociomedical Aspects. Edited by: vom Dahl S, Wendel U, Strohmeyer G. 2007, Cologne: Deutscher Arzte-Verlag, 13-18."},{"key":"26_CR3","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.mehy.2003.12.027","volume":"62","author":"G W\u0119grzyn","year":"2004","unstructured":"W\u0119grzyn G, W\u0119grzyn A, Tylki-Szyma\u0144ska A: A general model for genetic regulation of turnover of glycosaminoglycans suggests a possible procedure for prediction of severity and clinical progress of mucopolysaccharidoses. Med Hypoth. 2004, 62: 986-992.","journal-title":"Med Hypoth"},{"key":"26_CR4","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ymgme.2004.09.004","volume":"84","author":"M Fuller","year":"2005","unstructured":"Fuller M, Brooks DA, Evangelista M, Hein LK, Hopwood JJ, Meikle PJ: Prediction of neuropathology in mucopolysaccharidosis I patients. Mol Genet Metab. 2005, 84: 18-24.","journal-title":"Mol Genet Metab"},{"key":"26_CR5","volume-title":"Acta Paediatr","author":"E Piotrowska","year":"2009","unstructured":"Piotrowska E, Jak\u00f3bkiewicz-Banecka J, Tylki-Szyma\u0144ska A, Czartoryska B, W\u0119grzyn A, W\u0119grzyn G: Correlation between severity of mucopolysaccharidoses and combination of the residual enzyme activity and efficiency of glycosaminoglycan synthesis. Acta Paediatr. 2009,"},{"key":"26_CR6","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1056\/NEJM200101183440304","volume":"344","author":"ED Kakkis","year":"2001","unstructured":"Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, Passage M, Izykowski B, Phillips J, Doroshow R, Walot I, Hoft R, Neufeld EF: Enzyme-replacement therapy in mucopolysaccharidosis I. New Eng J Med. 2001, 344: 182-188.","journal-title":"New Eng J Med"},{"key":"26_CR7","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.jpeds.2004.01.046","volume":"144","author":"JE Wraith","year":"2004","unstructured":"Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Swiedler SJ, Kakkis ED, Braakman T, Chadbourne E, Walton-Bowen K, Cox GF: Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human \u03b1-L-iduronidase (Laronidase). J Pediatr. 2004, 144: 581-588.","journal-title":"J Pediatr"},{"key":"26_CR8","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.jpeds.2005.12.014","volume":"148","author":"P Harmatz","year":"2006","unstructured":"Harmatz P, Giugliani R, Schwartz I, Guffon N, Teles EL, Miranda MC, Wraith JE, Beck M, Arash L, Scarpa M, Yu ZF, Wittes J, Berger KI, Newman MS, Lowe AM, Kakkis E, Swiedler SJ, MPS VI Phase 3 Study Group: Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr. 2006, 148: 533-539.","journal-title":"J Pediatr"},{"key":"26_CR9","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1097\/01.gim.0000232477.37660.fb","volume":"8","author":"J Muenzer","year":"2006","unstructured":"Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A: A phase II\/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006, 8: 465-473.","journal-title":"Genet Med"},{"key":"26_CR10","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.ymgme.2006.08.007","volume":"90","author":"M Sifuentes","year":"2007","unstructured":"Sifuentes M, Doroshow R, Hoft R, Mason G, Walot I, Diament M, Okazaki S, Huff K, Cox GF, Swiedler SJ, Kakkis ED: A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years. Mol Genet Metab. 2007, 90: 171-180.","journal-title":"Mol Genet Metab"},{"key":"26_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00439-006-0280-4","volume":"121","author":"M Beck","year":"2007","unstructured":"Beck M: New therapeutic options for lysosomal storage disorders: enzyme replacement, small molecules and gene therapy. Hum Genet. 2007, 121: 1-22.","journal-title":"Hum Genet"},{"key":"26_CR12","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1203\/01.pdr.0000233037.00707.da","volume":"60","author":"AL Roberts","year":"2006","unstructured":"Roberts AL, Thomas BJ, Wilkinson AS, Fletcher JM, Byers S: Inhibition of glycosaminoglycan synthesis using rhodamine B in a mouse model of mucopolysaccharidosis type IIIA. Pediatr Res. 2006, 60: 309-314.","journal-title":"Pediatr Res"},{"key":"26_CR13","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ymgme.2007.06.016","volume":"92","author":"AL Roberts","year":"2007","unstructured":"Roberts AL, Rees MH, Klebe S, Fletcher JM, Byers S: Improvement in behaviour after substrate deprivation therapy with rhodamine B in a mouse model of MPS IIIA. Mol Genet Metab. 2007, 92: 115-121.","journal-title":"Mol Genet Metab"},{"key":"26_CR14","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/sj.ejhg.5201623","volume":"14","author":"E Piotrowska","year":"2006","unstructured":"Piotrowska E, Jak\u00f3bkiewicz-Banecka J, Bara\u0144ska S, Tylki-Szyma\u0144ska A, Czartoryska B, Wegrzyn A, Wegrzyn G: Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. Eur J Hum Genet. 2006, 14: 846-852.","journal-title":"Eur J Hum Genet"},{"key":"26_CR15","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.curtheres.2008.04.002","volume":"69","author":"E Piotrowska","year":"2008","unstructured":"Piotrowska E, Jak\u00f3bkiewicz-Banecka J, Tylki-Szyma\u0144ska A, Liberek A, Maryniak A, Malinowska M, Czartoryska B, Puk E, Kloska A, Liberek T, Bara\u0144ska S, W\u0119grzyn A, W\u0119grzyn G: Genistin-rich isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: an open-label, pilot study in 10 pediatric patients. Curr Ther Res Clin Exp. 2008, 69: 166-179.","journal-title":"Curr Ther Res Clin Exp"},{"key":"26_CR16","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/BF03195237","volume":"48","author":"J Jak\u00f3bkiewicz-Banecka","year":"2007","unstructured":"Jak\u00f3bkiewicz-Banecka J, Wegrzyn A, Wegrzyn G: Substrate deprivation therapy: A new hope for patients suffering from neuronopathic forms of inherited lysosomal storage diseases. J Appl Genet. 2007, 48: 383-388.","journal-title":"J Appl Genet"},{"key":"26_CR17","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/0012-1606(87)90306-X","volume":"122","author":"MM Pisano","year":"1987","unstructured":"Pisano MM, Greene RM: Epidermal growth factor potentiates the induction of ornithine decarboxylase activity by prostaglandins in embryonic palate mesenchymal cells: effects on cell proliferation and glycosaminoglycan synthesis. Dev Biol. 1987, 122: 419-431.","journal-title":"Dev Biol"},{"key":"26_CR18","doi-asserted-by":"publisher","first-page":"4787","DOI":"10.1074\/jbc.272.8.4787","volume":"272","author":"E Tirone","year":"1997","unstructured":"Tirone E, D'Alessandris C, Hascall VC, Siracusa G, Salustri A: Hyaluronan synthesis by mouse cumulus cells is regulated by interactions between folicle-stimulating hormone (or epidermal growth factor) and a soluble oocyte factor (or transforming growth factor \u03b21). J Biol Chem. 1997, 272: 4787-4794.","journal-title":"J Biol Chem"},{"key":"26_CR19","first-page":"1","volume":"327","author":"F Edwin","year":"2006","unstructured":"Edwin F, Wiepz GJ, Singh R, Peet CR, Chaturvedi D, Bertics PJ, Patel TB: A historical perspective of the EGF receptor and related systems. Methods Mol Biol. 2006, 327: 1-24.","journal-title":"Methods Mol Biol"},{"key":"26_CR20","doi-asserted-by":"crossref","first-page":"5592","DOI":"10.1016\/S0021-9258(18)45614-1","volume":"262","author":"T Akiyama","year":"1987","unstructured":"Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, Shibuya M, Fukami Y: Genistein, a specific inhibitor of tyrosine-specific protein kinase. J Biol Chem. 1987, 262: 5592-5595.","journal-title":"J Biol Chem"},{"issue":"Suppl","key":"26_CR21","doi-asserted-by":"crossref","first-page":"1418S","DOI":"10.1093\/ajcn\/68.6.1418S","volume":"68","author":"H Kim","year":"1998","unstructured":"Kim H, Peterson TG, Barnes S: Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor beta signaling pathways. J Clin Nutr. 1998, 68 (Suppl): 1418S-1425S.","journal-title":"J Clin Nutr"},{"key":"26_CR22","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jsbmb.2007.01.005","volume":"105","author":"K Szkudelska","year":"2007","unstructured":"Szkudelska K, Nogowski L: Genistein \u2013 a dietary compound inducing hormonal and metabolic changes. J Steroid Biochem Mol Biol. 2007, 105: 37-45.","journal-title":"J Steroid Biochem Mol Biol"},{"key":"26_CR23","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/S0003-9861(03)00129-2","volume":"413","author":"M Murata","year":"2003","unstructured":"Murata M, Bonassar LJ, Wright M, Mankin HJ, Towle CA: A role for the interleukin-1 receptor in the pathway linking static mechanical compression to decreased proteoglycan synthesis in surface articular cartilage. Arch Biochem Biophys. 2003, 413: 229-235.","journal-title":"Arch Biochem Biophys"},{"key":"26_CR24","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/9780470110249.ch4","volume":"8","author":"JE Scott","year":"1960","unstructured":"Scott JE: Aliphatic ammonium salts in the assay of acidic polysaccharides from tissues. Methods Biochem Anal. 1960, 8: 145-197.","journal-title":"Methods Biochem Anal"},{"key":"26_CR25","doi-asserted-by":"publisher","first-page":"5828","DOI":"10.1158\/0008-5472.CAN-06-0139","volume":"66","author":"A Herman-Antosiewicz","year":"2006","unstructured":"Herman-Antosiewicz A, Johnson DE, Singh SV: Sulforaphane causes autophagy to inhibit release of cytochrome c and apoptosis in human prostate cancer cells. Cancer Res. 2006, 66: 5828-5835.","journal-title":"Cancer Res"},{"key":"26_CR26","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1196\/annals.1397.048","volume":"1095","author":"V Jefremov","year":"2007","unstructured":"Jefremov V, Zilmer M, Zilmer K, Bogdanovic N, Karelson E: Antioxidative effects of plant polyphenols: from protection of G protein signaling to prevention of age-related pathologies. Ann N Y Acad Sci. 2007, 1095: 449-457.","journal-title":"Ann N Y Acad Sci"},{"key":"26_CR27","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1002\/jnr.21134","volume":"85","author":"GR Villani","year":"2007","unstructured":"Villani GR, Gargiulo N, Faraonio R, Castaldo S, Gonzalez Y, Reyero E, Di Natale P: Cytokines, neurotrophins, and oxidative stress in brain disease from mucopolysaccharidosis IIIB. J Neurosci Res. 2007, 85: 612-622.","journal-title":"J Neurosci Res"},{"key":"26_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.taap.2007.06.022","volume":"224","author":"CB Klein","year":"2007","unstructured":"Klein CB, King AA: Genistein genotoxity: critical considerations of in vitro exposure dose. Toxicol Appl Pharmacol. 2007, 224: 1-11.","journal-title":"Toxicol Appl Pharmacol"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1423-0127-16-26.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T01:25:49Z","timestamp":1630459549000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/1423-0127-16-26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,2]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["26"],"URL":"https:\/\/doi.org\/10.1186\/1423-0127-16-26","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,2]]},"assertion":[{"value":"18 July 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2009","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2009","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"26"}}