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dc.contributor.author
Veiras, Luciana Cecilia
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dc.contributor.author
Shen, Justin Z. Y.
dc.contributor.author
Bernstein, Ellen A.
dc.contributor.author
Regis, Giovanna C.
dc.contributor.author
Cao, DuoYao
dc.contributor.author
Okwan Duodu, Derick
dc.contributor.author
Khan, Zakir
dc.contributor.author
Gibb, David R.
dc.contributor.author
Dominici, Fernando Pablo
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dc.contributor.author
Bernstein, Kenneth E.
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dc.contributor.author
Giani, Jorge Fernando
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dc.date.available
2023-01-02T16:43:44Z
dc.date.issued
2021-05
dc.identifier.citation
Veiras, Luciana Cecilia; Shen, Justin Z. Y.; Bernstein, Ellen A.; Regis, Giovanna C.; Cao, DuoYao; et al.; Renal inflammation induces salt sensitivity in male db/db mice through dysregulation of ENaC; Synthesis-Stuttgart; Journal of the American Society of Nephrology; 32; 5; 5-2021; 1131-1149
dc.identifier.issn
1046-6673
dc.identifier.uri
http://hdl.handle.net/11336/182921
dc.description.abstract
Background Hypertension is considered a major risk factor for the progression of diabetic kidney disease. Type 2 diabetes is associated with increased renal sodium reabsorption and salt-sensitive hypertension. Clinical studies show that men have higher risk than premenopausal women for the development of diabetic kidney disease. However, the renal mechanisms that predispose to salt sensitivity during diabetes and whether sexual dimorphism is associated with these mechanisms remains unknown. Methods Female and male db/db mice exposed to a high-salt diet were used to analyze the progression of diabetic kidney disease and the development of hypertension. Results Male, 34-week-old, db/db mice display hypertension when exposed to a 4-week high-salt treatment, whereas equivalently treated female db/db mice remain normotensive. Salt-sensitive hypertension in male mice was associated with no suppression of the epithelial sodium channel (ENaC) in response to a high-salt diet, despite downregulation of several components of the intrarenal renin-angiotensin system. Male db/db mice show higher levels of proinflammatory cytokines and more immune-cell infiltration in the kidney than do female db/db mice. Blocking inflammation, with either mycophenolate mofetil or by reducing IL-6 levels with a neutralizing anti-IL-6 antibody, prevented the development of salt sensitivity in male db/db mice. Conclusions The inflammatory response observed in male, but not in female, db/db mice induces salt-sensitive hypertension by impairing ENaC downregulation in response to high salt. These data provide a mechanistic explanation for the sexual dimorphism associated with the development of diabetic kidney disease and salt sensitivity.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Synthesis-Stuttgart
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
diabetes
dc.subject
renin angiotensin system
dc.subject
sex differences
dc.subject
sodium transporters
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Renal inflammation induces salt sensitivity in male db/db mice through dysregulation of ENaC
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-09-22T11:47:20Z
dc.journal.volume
32
dc.journal.number
5
dc.journal.pagination
1131-1149
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Veiras, Luciana Cecilia. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Shen, Justin Z. Y.. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Bernstein, Ellen A.. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Regis, Giovanna C.. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Cao, DuoYao. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Okwan Duodu, Derick. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Khan, Zakir. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Gibb, David R.. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Dominici, Fernando Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
dc.description.fil
Fil: Bernstein, Kenneth E.. Cedars Sinai Medical Center; Estados Unidos
dc.description.fil
Fil: Giani, Jorge Fernando. Cedars Sinai Medical Center; Estados Unidos
dc.journal.title
Journal of the American Society of Nephrology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://jasn.asnjournals.org/lookup/doi/10.1681/ASN.2020081112
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1681/ASN.2020081112
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