Genistein improves renal disease in a mouse model of nephropathic cystinosis: a comparison study with cysteamine.

Autor:	De Leo E; Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Taranta A; Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Raso R; Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Polishchuk E; Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy., D'Oria V; Research Laboratories, Confocal Microscopy Core Facility, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Pezzullo M; Core Facilities, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Goffredo BM; Department of Pediatric Specialties and Liver-Kidney Transplantation, Division of Metabolic Biochemistry and Drug Biology, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Cairoli S; Department of Pediatric Specialties and Liver-Kidney Transplantation, Division of Metabolic Biochemistry and Drug Biology, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Bellomo F; Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Battafarano G; Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Camassei FD; Department of Laboratories-Pathology Unit, Bambino Gesù Children's Hospital, 00165 Rome, Italy., Del Fattore A; Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Polishchuk R; Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy., Emma F; Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.; Division of Nephrology, Department of Pediatric Subspecialties, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy., Rega LR; Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2023 Mar 20; Vol. 32 (7), pp. 1090-1101.
DOI:	10.1093/hmg/ddac266
Abstrakt:	Cysteamine is currently the only therapy for nephropathic cystinosis. It significantly improves life expectancy and delays progression to end-stage kidney disease; however, it cannot prevent it. Unfortunately, compliance to therapy is often weak, particularly during adolescence. Therefore, finding better treatments is a priority in the field of cystinosis. Previously, we found that genistein, an isoflavone particularly enriched in soy, can revert part of the cystinotic cellular phenotype that is not sensitive to cysteamine in vitro. To test the effects of genistein in vivo, we fed 2-month-old wild-type and Ctns-/- female mice with either a control diet, a genistein-containing diet or a cysteamine-containing diet for 14 months. Genistein (160 mg/kg/day) did not affect the growth of the mice or hepatic functionality. Compared with untreated mice at 16 months, Ctns-/- mice fed with genistein had lower cystine concentrations in their kidneys, reduced formation of cystine crystals, a smaller number of LAMP1-positive structures and an overall better-preserved parenchymal architecture. Cysteamine (400 mg/kg/day) was efficient in reverting the lysosomal phenotype and in preventing the development of renal lesions. These preclinical data indicate that genistein ameliorates kidney injury resulting from cystinosis with no side effects. Genistein therapy represents a potential treatment to improve the outcome for patients with cystinosis. (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu