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Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice
ErbB4 is highly expressed in the cystic kidneys with polycystic kidney diseases. To investigate its potential role in cystogenesis, cpk mice carrying a heart-rescued ErbB4 deletion were generated. Accelerated cyst progression and renal function deterioration were noted as early as 10 days postnatall...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149866/ https://www.ncbi.nlm.nih.gov/pubmed/24670412 http://dx.doi.org/10.1038/ki.2014.84 |
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author | Zeng, Fenghua Miyazawa, Tomoki Kloepfer, Lance A. Harris, Raymond C. |
author_facet | Zeng, Fenghua Miyazawa, Tomoki Kloepfer, Lance A. Harris, Raymond C. |
author_sort | Zeng, Fenghua |
collection | PubMed |
description | ErbB4 is highly expressed in the cystic kidneys with polycystic kidney diseases. To investigate its potential role in cystogenesis, cpk mice carrying a heart-rescued ErbB4 deletion were generated. Accelerated cyst progression and renal function deterioration were noted as early as 10 days postnatally in cpk mice with ErbB4 deletion compared to cpk mice, as indicated by increased cystic index, higher kidney weight to body weight ratios and elevated BUN levels. No apparent defects in renal development were noted with ErbB4 deletion itself. Increased cell proliferation was predominately seen in the cortex of cystic kidneys with or without ErbB4 deletion. However, there was significantly more cell proliferation in the cyst-lining epithelial cells in cpk mice with ErbB4 deletion. TUNEL staining localized apoptotic cells mainly to the renal medulla. There were significantly more apoptotic cells in the cyst-lining epithelial cells in ErbB4-deleted cpk kidneys, with decreased levels of cyclin D1, increased levels of p21, p27 and cleaved caspase 3. Thus, lack of ErbB4 may contribute to elevated cell proliferation and unbalanced cell apoptosis, resulting in accelerated cyst formation and early renal function deterioration. These studies suggest that the high level of ErbB4 expression seen in cpk mice may exert relative cytoprotective effects in renal epithelia. |
format | Online Article Text |
id | pubmed-4149866 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-41498662015-03-01 Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice Zeng, Fenghua Miyazawa, Tomoki Kloepfer, Lance A. Harris, Raymond C. Kidney Int Article ErbB4 is highly expressed in the cystic kidneys with polycystic kidney diseases. To investigate its potential role in cystogenesis, cpk mice carrying a heart-rescued ErbB4 deletion were generated. Accelerated cyst progression and renal function deterioration were noted as early as 10 days postnatally in cpk mice with ErbB4 deletion compared to cpk mice, as indicated by increased cystic index, higher kidney weight to body weight ratios and elevated BUN levels. No apparent defects in renal development were noted with ErbB4 deletion itself. Increased cell proliferation was predominately seen in the cortex of cystic kidneys with or without ErbB4 deletion. However, there was significantly more cell proliferation in the cyst-lining epithelial cells in cpk mice with ErbB4 deletion. TUNEL staining localized apoptotic cells mainly to the renal medulla. There were significantly more apoptotic cells in the cyst-lining epithelial cells in ErbB4-deleted cpk kidneys, with decreased levels of cyclin D1, increased levels of p21, p27 and cleaved caspase 3. Thus, lack of ErbB4 may contribute to elevated cell proliferation and unbalanced cell apoptosis, resulting in accelerated cyst formation and early renal function deterioration. These studies suggest that the high level of ErbB4 expression seen in cpk mice may exert relative cytoprotective effects in renal epithelia. 2014-03-26 2014-09 /pmc/articles/PMC4149866/ /pubmed/24670412 http://dx.doi.org/10.1038/ki.2014.84 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Zeng, Fenghua Miyazawa, Tomoki Kloepfer, Lance A. Harris, Raymond C. Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice |
title | Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice |
title_full | Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice |
title_fullStr | Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice |
title_full_unstemmed | Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice |
title_short | Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice |
title_sort | deletion of erbb4 accelerates polycystic kidney disease progression in cpk mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149866/ https://www.ncbi.nlm.nih.gov/pubmed/24670412 http://dx.doi.org/10.1038/ki.2014.84 |
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