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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 (Pgc1\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms242115853","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T03:29:33Z","timestamp":1698809373000},"page":"15853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-6409","authenticated-orcid":false,"given":"Maria D.","family":"Sanchez-Ni\u00f1o","sequence":"first","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"},{"name":"RICORS2040, 28040 Madrid, Spain"},{"name":"Department of Pharmacology, School of Medicine, Universidad Autonoma de Madrid, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria I.","family":"Ceballos","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"},{"name":"RICORS2040, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-5279","authenticated-orcid":false,"given":"Sol","family":"Carriazo","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"},{"name":"RICORS2040, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aranzazu","family":"Pintor-Chocano","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"},{"name":"RICORS2040, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0255-5689","authenticated-orcid":false,"given":"Ana B.","family":"Sanz","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"},{"name":"RICORS2040, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9808-4518","authenticated-orcid":false,"given":"Moin A.","family":"Saleem","sequence":"additional","affiliation":[{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1UD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-9523","authenticated-orcid":false,"given":"Alberto","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain"},{"name":"RICORS2040, 28040 Madrid, Spain"},{"name":"Department of Medicine, School of Medicine, Universidad Autonoma de Madrid, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","article-title":"Fabry disease revisited: Management and treatment recommendations for adult patients","volume":"123","author":"Ortiz","year":"2018","journal-title":"Mol. 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