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Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death
Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by deficiency of polycystin-1 (PC1) or polycystin-2 (PC2). Altered autophagy has recently been implicated in ADPKD progression, but its exact regulation by PC1 and PC2 remains unclear. We therefore investigated cell death and surv...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706473/ https://www.ncbi.nlm.nih.gov/pubmed/34948309 http://dx.doi.org/10.3390/ijms222413511 |
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author | Decuypere, Jean-Paul Van Giel, Dorien Janssens, Peter Dong, Ke Somlo, Stefan Cai, Yiqiang Mekahli, Djalila Vennekens, Rudi |
author_facet | Decuypere, Jean-Paul Van Giel, Dorien Janssens, Peter Dong, Ke Somlo, Stefan Cai, Yiqiang Mekahli, Djalila Vennekens, Rudi |
author_sort | Decuypere, Jean-Paul |
collection | PubMed |
description | Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by deficiency of polycystin-1 (PC1) or polycystin-2 (PC2). Altered autophagy has recently been implicated in ADPKD progression, but its exact regulation by PC1 and PC2 remains unclear. We therefore investigated cell death and survival during nutritional stress in mouse inner medullary collecting duct cells (mIMCDs), either wild-type (WT) or lacking PC1 (PC1KO) or PC2 (PC2KO), and human urine-derived proximal tubular epithelial cells (PTEC) from early-stage ADPKD patients with PC1 mutations versus healthy individuals. Basal autophagy was enhanced in PC1-deficient cells. Similarly, following starvation, autophagy was enhanced and cell death reduced when PC1 was reduced. Autophagy inhibition reduced cell death resistance in PC1KO mIMCDs to the WT level, implying that PC1 promotes autophagic cell survival. Although PC2 expression was increased in PC1KO mIMCDs, PC2 knockdown did not result in reduced autophagy. PC2KO mIMCDs displayed lower basal autophagy, but more autophagy and less cell death following chronic starvation. This could be reversed by overexpression of PC1 in PC2KO. Together, these findings indicate that PC1 levels are partially coupled to PC2 expression, and determine the transition from renal cell survival to death, leading to enhanced survival of ADPKD cells during nutritional stress. |
format | Online Article Text |
id | pubmed-8706473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87064732021-12-25 Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death Decuypere, Jean-Paul Van Giel, Dorien Janssens, Peter Dong, Ke Somlo, Stefan Cai, Yiqiang Mekahli, Djalila Vennekens, Rudi Int J Mol Sci Article Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by deficiency of polycystin-1 (PC1) or polycystin-2 (PC2). Altered autophagy has recently been implicated in ADPKD progression, but its exact regulation by PC1 and PC2 remains unclear. We therefore investigated cell death and survival during nutritional stress in mouse inner medullary collecting duct cells (mIMCDs), either wild-type (WT) or lacking PC1 (PC1KO) or PC2 (PC2KO), and human urine-derived proximal tubular epithelial cells (PTEC) from early-stage ADPKD patients with PC1 mutations versus healthy individuals. Basal autophagy was enhanced in PC1-deficient cells. Similarly, following starvation, autophagy was enhanced and cell death reduced when PC1 was reduced. Autophagy inhibition reduced cell death resistance in PC1KO mIMCDs to the WT level, implying that PC1 promotes autophagic cell survival. Although PC2 expression was increased in PC1KO mIMCDs, PC2 knockdown did not result in reduced autophagy. PC2KO mIMCDs displayed lower basal autophagy, but more autophagy and less cell death following chronic starvation. This could be reversed by overexpression of PC1 in PC2KO. Together, these findings indicate that PC1 levels are partially coupled to PC2 expression, and determine the transition from renal cell survival to death, leading to enhanced survival of ADPKD cells during nutritional stress. MDPI 2021-12-16 /pmc/articles/PMC8706473/ /pubmed/34948309 http://dx.doi.org/10.3390/ijms222413511 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Decuypere, Jean-Paul Van Giel, Dorien Janssens, Peter Dong, Ke Somlo, Stefan Cai, Yiqiang Mekahli, Djalila Vennekens, Rudi Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death |
title | Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death |
title_full | Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death |
title_fullStr | Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death |
title_full_unstemmed | Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death |
title_short | Interdependent Regulation of Polycystin Expression Influences Starvation-Induced Autophagy and Cell Death |
title_sort | interdependent regulation of polycystin expression influences starvation-induced autophagy and cell death |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706473/ https://www.ncbi.nlm.nih.gov/pubmed/34948309 http://dx.doi.org/10.3390/ijms222413511 |
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