Striatin heterozygous mice are more sensitive to aldosterone-induced injury

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dc.contributor.authorGarza, Amanda E.
dc.contributor.authorTrefts, Elijah
dc.contributor.authorRangel, Isis A. Katayama
dc.contributor.authorBrooks, Danielle
dc.contributor.authorBaudrand, Rene
dc.contributor.authorMoize, Burhanuddin
dc.contributor.authorRomero, Jose R.
dc.contributor.authorRanjit, Sanjay
dc.contributor.authorTreesaranuwattana, Thitinan
dc.contributor.authorYao, Tham M.
dc.contributor.authorAdler, Gail K.
dc.contributor.authorPojoga, Luminita H.
dc.contributor.authorWilliams, Gordon H.
dc.date.accessioned2025-01-23T19:48:39Z
dc.date.available2025-01-23T19:48:39Z
dc.date.issued2020
dc.description.abstractAldosterone modulates the activity of both epithelial (specifically renal) and non-epithelial cells. Binding to the mineralocorticoid receptor (MR), activates two pathways: the classical genomic and the rapidly activated non-genomic that is substantially modulated by the level of striatin. We hypothesized that disruption of MR's non-genomic pathway would alter aldosterone-induced cardiovascular/renal damage. To test this hypothesis, wild type (WT) and striatin heterozygous knockout (Strn(+/-)) littermate male mice were fed a liberal sodium (1.6% Na+) diet and randomized to either protocol one: 3 weeks of treatment with either vehicle or aldosterone plus/minus MR antagonists, eplerenone or esaxerenone or protocol two: 2 weeks of treatment with either vehicle or L-NAME/Angll plus/minus MR antagonists, spironolactone or esaxerenone. Compared to the WT mice, basally, the Strn(+/-) mice had greater (similar to 26%) estimated renal glomeruli volume and reduced non-genomic second messenger signaling (pAkt/Akt ratio) in kidney tissue. In response to active treatment, the striatin-associated-cardiovascular/renal damage was limited to volume effects induced by aldosterone infusion: significantly increased blood pressure (BP) and albuminuria. In contrast, with aldosterone or L-NAME/Angll treatment, striatin deficiency did not modify aldosterone-mediated damage: in the heart and kidney, macrophage infiltration, and increases in aldosterone-induced biomarkers of injury. All changes were near-normalized following MR blockade with spironolactone or esaxerenone, except increased BP in the L-NAME/Angll model. In conclusion, the loss of striatin amplified aldosterone-induced damage suggesting that aldosterone's non-genomic pathway is protective but only related to effects likely mediated via epithelial, but not non-epithelial cells.
dc.fuente.origenWOS
dc.identifier.doi10.1530/JOE-19-0562
dc.identifier.eissn1479-6805
dc.identifier.issn0022-0795
dc.identifier.urihttps://doi.org/10.1530/JOE-19-0562
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100456
dc.identifier.wosidWOS:000566408200009
dc.issue.numero3
dc.language.isoen
dc.pagina.final450
dc.pagina.inicio439
dc.revistaJournal of endocrinology
dc.rightsacceso restringido
dc.subjectmineralocorticoid receptor antagonist
dc.subjectaldosterone
dc.subjectcardiac and renal injury
dc.subjectnon-genomic
dc.subjectstriatin
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleStriatin heterozygous mice are more sensitive to aldosterone-induced injury
dc.typeartículo
dc.volumen245
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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