Hypoxia induces polycystin-1 expression in the renal epithelium
Mutations in polycystin-1 which is encoded by the PKD1 gene are the main causes for the development of autosomal dominant polycystic kidney disease. However, only little is known about the physiological function of polycystin-1 and even less about the regulation of its expression. Here, we show that...
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| Format: | Article |
| Language: | English |
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The Royal Society
2023-05-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.220992 |
| _version_ | 1827946036572717056 |
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| author | Steffen Grampp Andre Kraus Kathrin Skoczynski Mario Schiffer René Krüger Stephanie Naas Johannes Schödel Bjoern Buchholz |
| author_facet | Steffen Grampp Andre Kraus Kathrin Skoczynski Mario Schiffer René Krüger Stephanie Naas Johannes Schödel Bjoern Buchholz |
| author_sort | Steffen Grampp |
| collection | DOAJ |
| description | Mutations in polycystin-1 which is encoded by the PKD1 gene are the main causes for the development of autosomal dominant polycystic kidney disease. However, only little is known about the physiological function of polycystin-1 and even less about the regulation of its expression. Here, we show that expression of PKD1 is induced by hypoxia and compounds that stabilize the hypoxia-inducible transcription factor (HIF) 1α in primary human tubular epithelial cells. Knockdown of HIF subunits confirms HIF-1α-dependent regulation of polycystin-1 expression. Furthermore, HIF ChIP-seq reveals that HIF interacts with a regulatory DNA element within the PKD1 gene in renal tubule-derived cells. HIF-dependent expression of polycystin-1 can also be demonstrated in vivo in kidneys of mice treated with substances that stabilize HIF. Polycystin-1 and HIF-1α have been shown to promote epithelial branching during kidney development. In line with these findings, we show that expression of polycystin-1 within mouse embryonic ureteric bud branches is regulated by HIF. Our finding links expression of one of the main regulators of accurate renal development with the hypoxia signalling pathway and provides additional insight into the pathophysiology of polycystic kidney disease. |
| first_indexed | 2024-03-13T10:53:03Z |
| format | Article |
| id | doaj.art-24bffbf1ba6a4e1fb306b49c95f82682 |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-03-13T10:53:03Z |
| publishDate | 2023-05-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-24bffbf1ba6a4e1fb306b49c95f826822023-05-17T07:27:24ZengThe Royal SocietyRoyal Society Open Science2054-57032023-05-0110510.1098/rsos.220992Hypoxia induces polycystin-1 expression in the renal epitheliumSteffen Grampp0Andre Kraus1Kathrin Skoczynski2Mario Schiffer3René Krüger4Stephanie Naas5Johannes Schödel6Bjoern Buchholz7Department of Nephrology and Hypertension, Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Nephrology and Hypertension, Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Nephrology and Hypertension, Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Nephrology and Hypertension, Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Nephrology and Hypertension, Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Nephrology and Hypertension, Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Nephrology and Hypertension, Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Nephrology and Hypertension, Uniklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyMutations in polycystin-1 which is encoded by the PKD1 gene are the main causes for the development of autosomal dominant polycystic kidney disease. However, only little is known about the physiological function of polycystin-1 and even less about the regulation of its expression. Here, we show that expression of PKD1 is induced by hypoxia and compounds that stabilize the hypoxia-inducible transcription factor (HIF) 1α in primary human tubular epithelial cells. Knockdown of HIF subunits confirms HIF-1α-dependent regulation of polycystin-1 expression. Furthermore, HIF ChIP-seq reveals that HIF interacts with a regulatory DNA element within the PKD1 gene in renal tubule-derived cells. HIF-dependent expression of polycystin-1 can also be demonstrated in vivo in kidneys of mice treated with substances that stabilize HIF. Polycystin-1 and HIF-1α have been shown to promote epithelial branching during kidney development. In line with these findings, we show that expression of polycystin-1 within mouse embryonic ureteric bud branches is regulated by HIF. Our finding links expression of one of the main regulators of accurate renal development with the hypoxia signalling pathway and provides additional insight into the pathophysiology of polycystic kidney disease.https://royalsocietypublishing.org/doi/10.1098/rsos.220992polycystic kidney diseasePKD1transcription regulationhypoxiahypoxia-inducible factorkidney development |
| spellingShingle | Steffen Grampp Andre Kraus Kathrin Skoczynski Mario Schiffer René Krüger Stephanie Naas Johannes Schödel Bjoern Buchholz Hypoxia induces polycystin-1 expression in the renal epithelium Royal Society Open Science polycystic kidney disease PKD1 transcription regulation hypoxia hypoxia-inducible factor kidney development |
| title | Hypoxia induces polycystin-1 expression in the renal epithelium |
| title_full | Hypoxia induces polycystin-1 expression in the renal epithelium |
| title_fullStr | Hypoxia induces polycystin-1 expression in the renal epithelium |
| title_full_unstemmed | Hypoxia induces polycystin-1 expression in the renal epithelium |
| title_short | Hypoxia induces polycystin-1 expression in the renal epithelium |
| title_sort | hypoxia induces polycystin 1 expression in the renal epithelium |
| topic | polycystic kidney disease PKD1 transcription regulation hypoxia hypoxia-inducible factor kidney development |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.220992 |
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