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• W3211105320 endingPage "1717" @default.
• W3211105320 startingPage "1717" @default.
• W3211105320 abstract "Wolfram syndrome (WS) 1 is a rare monogenic neurodegenerative disorder caused by mutations in the gene encoding WFS1. Knowledge of the pathophysiology of WS is incomplete and to date, there is no treatment available. Here, we describe early deviations in the renin-angiotensin-aldosterone system (RAAS) and bradykinin pathway (kallikrein kinin system, KKS) observed in a rat model of WS (Wfs1 KO) and the modulative effect of glucagon-like peptide-1 receptor agonist liraglutide (LIR) and anti-epileptic drug valproate (VPA), which have been proven effective in delaying WS progression in WS animal models. We found that the expression of key receptors of the RAAS and KKS, Agtr2 and Bdkrb1, were drastically downregulated both in vitro and in vivo at an early stage in a rat model of WS. Moreover, in Wfs1, KO serum aldosterone levels were substantially decreased and bradykinin levels increased compared to WT animals. Neither treatment nor their combination affected the gene expression levels seen in the Wfs1 KO animals. However, all the treatments elevated serum aldosterone and decreased bradykinin in the Wfs1 KO rats, as well as increasing angiotensin II levels independent of genotype. Altogether, our results indicate that Wfs1 deficiency might disturb the normal functioning of RAAS and KKS and that LIR and VPA have the ability to modulate these systems." @default.
• W3211105320 created "2021-11-08" @default.
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• W3211105320 date "2021-10-28" @default.
• W3211105320 modified "2023-10-16" @default.
• W3211105320 title "The Expression of RAAS Key Receptors, Agtr2 and Bdkrb1, Is Downregulated at an Early Stage in a Rat Model of Wolfram Syndrome" @default.
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• W3211105320 doi "https://doi.org/10.3390/genes12111717" @default.
• W3211105320 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8621801" @default.
• W3211105320 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34828323" @default.
• W3211105320 hasPublicationYear "2021" @default.
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