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Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors

Fabry disease is a lysosomal disease characterized by globotriaosylceramide (Gb3) accumulation. It may coexist with diabetes mellitus and both cause potentially lethal kidney end-organ damage. However, there is little information on their interaction with kidney disease. We have addressed the intera...

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Autores principales: Sanchez-Niño, Maria D., Ceballos, Maria I., Carriazo, Sol, Pintor-Chocano, Aranzazu, Sanz, Ana B., Saleem, Moin A., Ortiz, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650640/
https://www.ncbi.nlm.nih.gov/pubmed/37958836
http://dx.doi.org/10.3390/ijms242115853
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author Sanchez-Niño, Maria D.
Ceballos, Maria I.
Carriazo, Sol
Pintor-Chocano, Aranzazu
Sanz, Ana B.
Saleem, Moin A.
Ortiz, Alberto
author_facet Sanchez-Niño, Maria D.
Ceballos, Maria I.
Carriazo, Sol
Pintor-Chocano, Aranzazu
Sanz, Ana B.
Saleem, Moin A.
Ortiz, Alberto
author_sort Sanchez-Niño, Maria D.
collection PubMed
description Fabry disease is a lysosomal disease characterized by globotriaosylceramide (Gb3) accumulation. It may coexist with diabetes mellitus and both cause potentially lethal kidney end-organ damage. However, there is little information on their interaction with kidney disease. We have addressed the interaction between Fabry disease and diabetes in data mining of human kidney transcriptomics databases and in Fabry (Gla-/-) and wild type mice with or without streptozotocin-induced diabetes. Data mining was consistent with differential expression of genes encoding enzymes from the Gb3 metabolic pathway in human diabetic kidney disease, including upregulation of UGCG, the gene encoding the upstream and rate-limiting enzyme glucosyl ceramide synthase. Diabetic Fabry mice displayed the most severe kidney infiltration by F4/80+ macrophages, and a lower kidney expression of kidney protective genes (Pgc1α and Tfeb) than diabetic wild type mice, without a further increase in kidney fibrosis. Moreover, only diabetic Fabry mice developed kidney insufficiency and these mice with kidney insufficiency had a high expression of Ugcg. In conclusion, we found evidence of interaction between diabetes and Fabry disease that may increase the severity of the kidney phenotype through modulation of the Gb3 synthesis pathway and downregulation of kidney protective genes.
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spelling pubmed-106506402023-11-01 Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors Sanchez-Niño, Maria D. Ceballos, Maria I. Carriazo, Sol Pintor-Chocano, Aranzazu Sanz, Ana B. Saleem, Moin A. Ortiz, Alberto Int J Mol Sci Article Fabry disease is a lysosomal disease characterized by globotriaosylceramide (Gb3) accumulation. It may coexist with diabetes mellitus and both cause potentially lethal kidney end-organ damage. However, there is little information on their interaction with kidney disease. We have addressed the interaction between Fabry disease and diabetes in data mining of human kidney transcriptomics databases and in Fabry (Gla-/-) and wild type mice with or without streptozotocin-induced diabetes. Data mining was consistent with differential expression of genes encoding enzymes from the Gb3 metabolic pathway in human diabetic kidney disease, including upregulation of UGCG, the gene encoding the upstream and rate-limiting enzyme glucosyl ceramide synthase. Diabetic Fabry mice displayed the most severe kidney infiltration by F4/80+ macrophages, and a lower kidney expression of kidney protective genes (Pgc1α and Tfeb) than diabetic wild type mice, without a further increase in kidney fibrosis. Moreover, only diabetic Fabry mice developed kidney insufficiency and these mice with kidney insufficiency had a high expression of Ugcg. In conclusion, we found evidence of interaction between diabetes and Fabry disease that may increase the severity of the kidney phenotype through modulation of the Gb3 synthesis pathway and downregulation of kidney protective genes. MDPI 2023-11-01 /pmc/articles/PMC10650640/ /pubmed/37958836 http://dx.doi.org/10.3390/ijms242115853 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sanchez-Niño, Maria D.
Ceballos, Maria I.
Carriazo, Sol
Pintor-Chocano, Aranzazu
Sanz, Ana B.
Saleem, Moin A.
Ortiz, Alberto
Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors
title Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors
title_full Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors
title_fullStr Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors
title_full_unstemmed Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors
title_short Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors
title_sort interaction of fabry disease and diabetes mellitus: suboptimal recruitment of kidney protective factors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650640/
https://www.ncbi.nlm.nih.gov/pubmed/37958836
http://dx.doi.org/10.3390/ijms242115853
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