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Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation
Inversion of embryonic turning (inv) cystic mice develop multiple renal cysts and are a model for type II nephronophthisis (NPHP2). The defect of planar cell polarity (PCP) by oriented cell division was proposed as the underlying cellular phenotype, while abnormal cell proliferation and apoptosis oc...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995398/ https://www.ncbi.nlm.nih.gov/pubmed/29889867 http://dx.doi.org/10.1371/journal.pone.0198580 |
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author | Shigeta, Masaki Kanazawa, Hirotaka Yokoyama, Takahiko |
author_facet | Shigeta, Masaki Kanazawa, Hirotaka Yokoyama, Takahiko |
author_sort | Shigeta, Masaki |
collection | PubMed |
description | Inversion of embryonic turning (inv) cystic mice develop multiple renal cysts and are a model for type II nephronophthisis (NPHP2). The defect of planar cell polarity (PCP) by oriented cell division was proposed as the underlying cellular phenotype, while abnormal cell proliferation and apoptosis occur in some polycystic kidney disease models. However, how these cystogenic phenotypes are linked and what is most critical for cystogenesis remain largely unknown. In particular, in early cortical cytogenesis in the inv mutant cystic model, it remains uncertain whether the increased proliferation index results from changes in cell cycle length or cell fate determination. To address tubular cell kinetics, doubling time and total number of tubular cells, as well as amount of genomic DNA (gDNA), were measured in mutant and normal control kidneys. Despite a significantly higher bromodeoxyuridine (BrdU)-proliferation index in the mutant, total tubular cell number and doubling time were unaffected. Unexpectedly, the mutant had tubular cell loss, characterized by a temporal decrease in tubular cells incorporating 5-ethynyl-2´-deoxyuridine (EdU) and significantly increased nuclear debris. Based on current data we established a new multi-population shift model in postnatal renal development, indicating that a few restricted tubular cell populations contribute to cortical tubular formation. As in the inv mutant phenotype, the model simulation revealed a large population of tubular cells with rapid cell cycling and tubular cell loss. The proposed cellular kinetics suggest not only the underlying mechanism of the inv mutant phenotype but also a possible renal homeostatic mechanism for tubule formation. |
format | Online Article Text |
id | pubmed-5995398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-59953982018-06-21 Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation Shigeta, Masaki Kanazawa, Hirotaka Yokoyama, Takahiko PLoS One Research Article Inversion of embryonic turning (inv) cystic mice develop multiple renal cysts and are a model for type II nephronophthisis (NPHP2). The defect of planar cell polarity (PCP) by oriented cell division was proposed as the underlying cellular phenotype, while abnormal cell proliferation and apoptosis occur in some polycystic kidney disease models. However, how these cystogenic phenotypes are linked and what is most critical for cystogenesis remain largely unknown. In particular, in early cortical cytogenesis in the inv mutant cystic model, it remains uncertain whether the increased proliferation index results from changes in cell cycle length or cell fate determination. To address tubular cell kinetics, doubling time and total number of tubular cells, as well as amount of genomic DNA (gDNA), were measured in mutant and normal control kidneys. Despite a significantly higher bromodeoxyuridine (BrdU)-proliferation index in the mutant, total tubular cell number and doubling time were unaffected. Unexpectedly, the mutant had tubular cell loss, characterized by a temporal decrease in tubular cells incorporating 5-ethynyl-2´-deoxyuridine (EdU) and significantly increased nuclear debris. Based on current data we established a new multi-population shift model in postnatal renal development, indicating that a few restricted tubular cell populations contribute to cortical tubular formation. As in the inv mutant phenotype, the model simulation revealed a large population of tubular cells with rapid cell cycling and tubular cell loss. The proposed cellular kinetics suggest not only the underlying mechanism of the inv mutant phenotype but also a possible renal homeostatic mechanism for tubule formation. Public Library of Science 2018-06-11 /pmc/articles/PMC5995398/ /pubmed/29889867 http://dx.doi.org/10.1371/journal.pone.0198580 Text en © 2018 Shigeta et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Shigeta, Masaki Kanazawa, Hirotaka Yokoyama, Takahiko Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation |
title | Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation |
title_full | Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation |
title_fullStr | Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation |
title_full_unstemmed | Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation |
title_short | Tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation |
title_sort | tubular cell loss in early inv/nphp2 mutant kidneys represents a possible homeostatic mechanism in cortical tubular formation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995398/ https://www.ncbi.nlm.nih.gov/pubmed/29889867 http://dx.doi.org/10.1371/journal.pone.0198580 |
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