Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury
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...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2573 |
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| author | Andrea Sánchez-Navarro Miguel Ángel Martínez-Rojas Adrián Albarrán-Godinez Rosalba Pérez-Villalva Johan Auwerx Abigail de la Cruz Lilia G. Noriega Florencia Rosetti Norma A. Bobadilla |
| author_facet | Andrea Sánchez-Navarro Miguel Ángel Martínez-Rojas Adrián Albarrán-Godinez Rosalba Pérez-Villalva Johan Auwerx Abigail de la Cruz Lilia G. Noriega Florencia Rosetti Norma A. Bobadilla |
| author_sort | Andrea Sánchez-Navarro |
| collection | DOAJ |
| description | 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 NFκB signaling. |
| first_indexed | 2024-03-09T20:38:17Z |
| format | Article |
| id | doaj.art-c98d501ace064f0e87a2e65a2d0df6b5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:38:17Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c98d501ace064f0e87a2e65a2d0df6b52023-11-23T23:06:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235257310.3390/ijms23052573Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney InjuryAndrea Sánchez-Navarro0Miguel Ángel Martínez-Rojas1Adrián Albarrán-Godinez2Rosalba Pérez-Villalva3Johan Auwerx4Abigail de la Cruz5Lilia G. Noriega6Florencia Rosetti7Norma A. Bobadilla8Molecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City 14080, MexicoMolecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City 14080, MexicoMolecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City 14080, MexicoMolecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City 14080, MexicoLaboratory of Integrative Systems Physiology (LISP), Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, SwitzerlandImmunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City 14080, MexicoNutrition Physiology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City 14080, MexicoImmunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City 14080, MexicoMolecular Physiology Unit, Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México, Mexico City 14080, MexicoAcute 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 NFκB signaling.https://www.mdpi.com/1422-0067/23/5/2573histone deacetylaseNFkB signalingimmune cells infiltrationtubular injury |
| spellingShingle | Andrea Sánchez-Navarro Miguel Ángel Martínez-Rojas Adrián Albarrán-Godinez Rosalba Pérez-Villalva Johan Auwerx Abigail de la Cruz Lilia G. Noriega Florencia Rosetti Norma A. Bobadilla Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury International Journal of Molecular Sciences histone deacetylase NFkB signaling immune cells infiltration tubular injury |
| title | Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury |
| title_full | Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury |
| title_fullStr | Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury |
| title_full_unstemmed | Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury |
| title_short | Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury |
| title_sort | sirtuin 7 deficiency reduces inflammation and tubular damage induced by an episode of acute kidney injury |
| topic | histone deacetylase NFkB signaling immune cells infiltration tubular injury |
| url | https://www.mdpi.com/1422-0067/23/5/2573 |
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