Loss of PGC-1α in RPE induces mesenchymal transition and promotes retinal degeneration
| Autor: | Mariana Aparecida Brunini Rosales, Magali Saint-Geniez, Daisy Y. Shu, Jared Iacovelli |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Retinal degeneration Retinal pigment epithelium Ecology Chemistry Health Toxicology and Mutagenesis Mesenchymal stem cell Autophagy Transdifferentiation Plant Science Mitochondrion medicine.disease Biochemistry Genetics and Molecular Biology (miscellaneous) eye diseases Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Conditional gene knockout medicine sense organs Epithelial–mesenchymal transition |
| Zdroj: | Life Science Alliance. 2:e201800212 |
| ISSN: | 2575-1077 |
| Popis: | The retinal pigment epithelium (RPE) supports visual processing and photoreceptor homeostasis via energetically demanding cellular functions. Here, we describe the consequences of repressing peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α), a master regulator of mitochondrial function and biogenesis, on RPE epithelial integrity. The sustained silencing of PGC-1α in differentiating human RPE cells affected mitochondria/autophagy function, redox state, and impaired energy sensor activity ultimately inducing epithelial to mesenchymal transition (EMT). Adult conditional knockout of PGC-1 coactivators in mice resulted in rapid RPE dysfunction and transdifferentiation associated with severe photoreceptor degeneration. RPE anomalies were characteristic of autophagic defect and mesenchymal transition comparable with the ones observed in age-related macular degeneration. These findings demonstrate that PGC-1α is required to maintain the functional and phenotypic status of RPE by supporting the cells’ oxidative metabolism and autophagy-mediated repression of EMT. |
| Databáze: | OpenAIRE |
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