The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes
Epigenetic alterations contribute to the pathogenesis of chronic diseases such as diabetes mellitus. Previous studies of our group showed that diabetic conditions reduce the trimethylation of H3K27 in podocytes in a NIPP1- (nuclear inhibitor of protein phosphatase 1) and EZH2- (enhancer of zeste hom...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2475 |
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| author | Johanna Barth Ivonne Loeffler Tzvetanka Bondeva Marita Liebisch Gunter Wolf |
| author_facet | Johanna Barth Ivonne Loeffler Tzvetanka Bondeva Marita Liebisch Gunter Wolf |
| author_sort | Johanna Barth |
| collection | DOAJ |
| description | Epigenetic alterations contribute to the pathogenesis of chronic diseases such as diabetes mellitus. Previous studies of our group showed that diabetic conditions reduce the trimethylation of H3K27 in podocytes in a NIPP1- (nuclear inhibitor of protein phosphatase 1) and EZH2- (enhancer of zeste homolog 2) dependent manner. It has been previously reported that in differentiated podocytes, hypoxia decreases the expression of slit diaphragm proteins and promotes foot process effacement, thereby contributing to the progression of renal disease. The exact mechanisms are, however, not completely understood. The aim of this study was to analyze the role of hypoxia and HIFs (hypoxia-inducible factor) on epigenetic changes in podocytes affecting NIPP1, EZH2 and H3K27me3, in vitro and in vivo. In vivo studies were performed with mice exposed to 10% systemic hypoxia for 3 days or injected with 3,4-DHB (dihydroxybenzoate), a PHD (prolyl hydroxylase) inhibitor, 24 h prior analyses. Immunodetection of H3K27me3, NIPP1 and EZH2 in glomerular podocytes revealed, to the best of our knowledge for the first time, that hypoxic conditions and pharmacological HIFs activation significantly reduce the expression of NIPP1 and EZH2 and diminish H3K27 trimethylation. These findings are also supported by in vitro studies using murine-differentiated podocytes. |
| first_indexed | 2024-03-10T23:00:50Z |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:50Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-e35cbe14787f47f9b70329c8497071412023-11-19T09:41:53ZengMDPI AGBiomedicines2227-90592023-09-01119247510.3390/biomedicines11092475The Role of Hypoxia on the Trimethylation of H3K27 in PodocytesJohanna Barth0Ivonne Loeffler1Tzvetanka Bondeva2Marita Liebisch3Gunter Wolf4Department of Internal Medicine III, University Hospital Jena, Am Klinikum 1, 07747 Jena, GermanyDepartment of Internal Medicine III, University Hospital Jena, Am Klinikum 1, 07747 Jena, GermanyDepartment of Internal Medicine III, University Hospital Jena, Am Klinikum 1, 07747 Jena, GermanyDepartment of Internal Medicine III, University Hospital Jena, Am Klinikum 1, 07747 Jena, GermanyDepartment of Internal Medicine III, University Hospital Jena, Am Klinikum 1, 07747 Jena, GermanyEpigenetic alterations contribute to the pathogenesis of chronic diseases such as diabetes mellitus. Previous studies of our group showed that diabetic conditions reduce the trimethylation of H3K27 in podocytes in a NIPP1- (nuclear inhibitor of protein phosphatase 1) and EZH2- (enhancer of zeste homolog 2) dependent manner. It has been previously reported that in differentiated podocytes, hypoxia decreases the expression of slit diaphragm proteins and promotes foot process effacement, thereby contributing to the progression of renal disease. The exact mechanisms are, however, not completely understood. The aim of this study was to analyze the role of hypoxia and HIFs (hypoxia-inducible factor) on epigenetic changes in podocytes affecting NIPP1, EZH2 and H3K27me3, in vitro and in vivo. In vivo studies were performed with mice exposed to 10% systemic hypoxia for 3 days or injected with 3,4-DHB (dihydroxybenzoate), a PHD (prolyl hydroxylase) inhibitor, 24 h prior analyses. Immunodetection of H3K27me3, NIPP1 and EZH2 in glomerular podocytes revealed, to the best of our knowledge for the first time, that hypoxic conditions and pharmacological HIFs activation significantly reduce the expression of NIPP1 and EZH2 and diminish H3K27 trimethylation. These findings are also supported by in vitro studies using murine-differentiated podocytes.https://www.mdpi.com/2227-9059/11/9/2475hypoxiapodocyteH3K27me3epigeneticNIPP1nuclear inhibitor of protein phosphatase 1 |
| spellingShingle | Johanna Barth Ivonne Loeffler Tzvetanka Bondeva Marita Liebisch Gunter Wolf The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes Biomedicines hypoxia podocyte H3K27me3 epigenetic NIPP1 nuclear inhibitor of protein phosphatase 1 |
| title | The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes |
| title_full | The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes |
| title_fullStr | The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes |
| title_full_unstemmed | The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes |
| title_short | The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes |
| title_sort | role of hypoxia on the trimethylation of h3k27 in podocytes |
| topic | hypoxia podocyte H3K27me3 epigenetic NIPP1 nuclear inhibitor of protein phosphatase 1 |
| url | https://www.mdpi.com/2227-9059/11/9/2475 |
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