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Vegfa promoter gene hypermethylation at HIF1α binding site is an early contributor to CKD progression after renal ischemia by Sánchez-Navarro, Andrea (author);Pérez-Villalva, Rosalba (author);Murillo-de-Ozores, Adrián Rafael (author);Martínez-Rojas, Miguel Ángel (author);Rodríguez‐Aguilera, Jesús Rafael (author);González, Norma (author);Castañeda-Bueno, María (author);Gamba, Gerardo (author);Recillas-Targa, Félix (author);Bobadilla, Norma A. (author) is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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Chronic hypoxia is a major contributor to Chronic Kidney Disease (CKD) after Acute Kidney Injury (AKI). However, the temporal relation between the acute insult and maladaptive renal response to hypoxia remains unclear. In this study, we analyzed the time-course of renal hemodynamics, oxidative stress, inflammation, and fibrosis, as well as epigenetic modifications, with focus on HIF1α/VEGF signaling, in the AKI to CKD transition. Sham-operated, right nephrectomy (UNx), and UNx plus renal ischemia (IR + UNx) groups of rats were included and studied at 1, 2, 3, or 4 months. The IR + UNx group developed CKD characterized by progressive proteinuria, renal dysfunction, tubular proliferation, and fibrosis. At first month post-ischemia, there was a twofold significant increase in oxidative stress and reduction in global DNA methylation that was maintained throughout the study. __Hif1α__ and __Vegfa__ expression were depressed in the first and second-months post-ischemia, and then __Hif1α__ but not __Vegfa__ expression was recovered. Interestingly, hypermethylation of the __Vegfa__ promoter gene at the HIF1α binding site was found, since early stages of the CKD progression. Our findings su

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Author

Sánchez-Navarro, Andrea (author);Pérez-Villalva, Rosalba (author);Murillo-de-Ozores, Adrián Rafael (author);Martínez-Rojas, Miguel Ángel (author);Rodríguez‐Aguilera, Jesús Rafael (author);González, Norma (author);Castañeda-Bueno, María (author);Gamba, Gerardo (author);Recillas-Targa, Félix (author);Bobadilla, Norma A. (author)

Publisher

Springer Science and Business Media LLC

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)