Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury
Por:
Sanchez-Navarro, Andrea, Martinez-Rojas, Miguel Angel, Albarran-Godinez, Adrian, Perez-Villalva, Rosalba, Auwerx, Johan, de la Cruz, Abigail, Noriega, Lilia G., Rosetti, Florencia, Bobadilla, Norma A.
Publicada:
1 mar 2022
Resumen:
Acute kidney injury (AKI) is a public health problem worldwide. Sirtuins
are a family of seven NAD+-dependent deacylases, Overexpression of
Sirtuin 1, 3, and 5 protect against AKI. However, the role of Sirtuin 7
(Sirt7) in AKI is not known. Here, we analyzed how Sirt7 deficient mice
(KO-Sirt7) were affected by AKI. As expected, wild-type and Sirt7
heterozygotes mice that underwent renal ischemia/reperfusion (IR)
exhibited the characteristic hallmarks of AKI: renal dysfunction,
tubular damage, albuminuria, increased oxidative stress, and renal
inflammation. In contrast, the KO-Sirt7+IR mice were protected from AKI,
exhibiting lesser albuminuria and reduction in urinary biomarkers of
tubular damage, despite similar renal dysfunction. The renoprotection in
the Sirt7-KO+IR group was associated with reduced kidney weight, minor
expression of inflammatory cytokines and less renal infiltration of
inflammatory cells. This anti-inflammatory effect was related to
diminished p65 expression and in its active phosphorylation, as well as
by a reduction in p65 nuclear translocation. Sirt7 deficient mice are
protected from AKI, suggesting that this histone deacetylase promotes
tubular damage and renal inflammation. Therefore, our findings indicate
that Sirt7 inhibitors may be an attractive therapeutic target to reduce
NF kappa B signaling.
Filiaciones:
Sanchez-Navarro, Andrea:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City, 14080, Mexico
Departments of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14080, Mexico
Martinez-Rojas, Miguel Angel:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City, 14080, Mexico
Departments of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14080, Mexico
Albarran-Godinez, Adrian:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City, 14080, Mexico
Departments of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14080, Mexico
Perez-Villalva, Rosalba:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City, 14080, Mexico
Departments of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14080, Mexico
Auwerx, Johan:
Laboratory of Integrative Systems Physiology (LISP), Ecole Polytechnique Federale de Lausanne, Lausanne, CH-1015, Switzerland
de la Cruz, Abigail:
Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14080, Mexico
Noriega, Lilia G.:
Nutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14080, Mexico
Rosetti, Florencia:
Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14080, Mexico
Bobadilla, Norma A.:
Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City, 14080, Mexico
Departments of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, 14080, Mexico
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