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Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis
We have previously shown that the conditional deletion of either the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), or its opposing phosphatase, phosphatase and tensin homolog (PTEN), had distinct effects on lens growth and homeostasis. The deletion of p110α reduced the levels of p...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455000/ https://www.ncbi.nlm.nih.gov/pubmed/36078116 http://dx.doi.org/10.3390/cells11172708 |
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author | Sellitto, Caterina Li, Leping White, Thomas W. |
author_facet | Sellitto, Caterina Li, Leping White, Thomas W. |
author_sort | Sellitto, Caterina |
collection | PubMed |
description | We have previously shown that the conditional deletion of either the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), or its opposing phosphatase, phosphatase and tensin homolog (PTEN), had distinct effects on lens growth and homeostasis. The deletion of p110α reduced the levels of phosphorylated Akt and equatorial epithelial cell proliferation, and resulted in smaller transparent lenses in adult mice. The deletion of PTEN increased levels of phosphorylated Akt, altered lens sodium transport, and caused lens rupture and cataract. Here, we have generated conditional p110α/PTEN double-knockout mice, and evaluated epithelial cell proliferation and lens homeostasis. The double deletion of p110α and PTEN rescued the defect in lens size seen after the single knockout of p110α, but accelerated the lens rupture phenotype seen in PTEN single-knockout mice. Levels of phosphorylated Akt in double-knockout lenses were significantly higher than in wild-type lenses, but not as elevated as those reported for PTEN single-knockout lenses. These results showed that the double deletion of the p110α catalytic subunit of PI3K and its opposing phosphatase, PTEN, exacerbated the rupture defect seen in the single PTEN knockout and alleviated the growth defect observed in the single p110α knockout. Thus, the integrity of the PI3K signaling pathway was absolutely essential for proper lens homeostasis, but not for lens growth. |
format | Online Article Text |
id | pubmed-9455000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94550002022-09-09 Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis Sellitto, Caterina Li, Leping White, Thomas W. Cells Article We have previously shown that the conditional deletion of either the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), or its opposing phosphatase, phosphatase and tensin homolog (PTEN), had distinct effects on lens growth and homeostasis. The deletion of p110α reduced the levels of phosphorylated Akt and equatorial epithelial cell proliferation, and resulted in smaller transparent lenses in adult mice. The deletion of PTEN increased levels of phosphorylated Akt, altered lens sodium transport, and caused lens rupture and cataract. Here, we have generated conditional p110α/PTEN double-knockout mice, and evaluated epithelial cell proliferation and lens homeostasis. The double deletion of p110α and PTEN rescued the defect in lens size seen after the single knockout of p110α, but accelerated the lens rupture phenotype seen in PTEN single-knockout mice. Levels of phosphorylated Akt in double-knockout lenses were significantly higher than in wild-type lenses, but not as elevated as those reported for PTEN single-knockout lenses. These results showed that the double deletion of the p110α catalytic subunit of PI3K and its opposing phosphatase, PTEN, exacerbated the rupture defect seen in the single PTEN knockout and alleviated the growth defect observed in the single p110α knockout. Thus, the integrity of the PI3K signaling pathway was absolutely essential for proper lens homeostasis, but not for lens growth. MDPI 2022-08-30 /pmc/articles/PMC9455000/ /pubmed/36078116 http://dx.doi.org/10.3390/cells11172708 Text en © 2022 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 Sellitto, Caterina Li, Leping White, Thomas W. Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis |
title | Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis |
title_full | Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis |
title_fullStr | Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis |
title_full_unstemmed | Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis |
title_short | Double Deletion of PI3K and PTEN Modifies Lens Postnatal Growth and Homeostasis |
title_sort | double deletion of pi3k and pten modifies lens postnatal growth and homeostasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455000/ https://www.ncbi.nlm.nih.gov/pubmed/36078116 http://dx.doi.org/10.3390/cells11172708 |
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