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Id Proteins Regulate Capillary Repair and Perivascular Cell Proliferation following Ischemia-Reperfusion Injury
Acute kidney injury (AKI) results in microvascular damage that if not normally repaired, may lead to fibrosis. The Id1 and 3 proteins have a critical role in promoting angiogenesis during development, tumor growth and wound repair by functioning as dominant negative regulators of bHLH transcription...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917915/ https://www.ncbi.nlm.nih.gov/pubmed/24516656 http://dx.doi.org/10.1371/journal.pone.0088417 |
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author | Lee, David Shenoy, Shantheri Nigatu, Yezina Plotkin, Matt |
author_facet | Lee, David Shenoy, Shantheri Nigatu, Yezina Plotkin, Matt |
author_sort | Lee, David |
collection | PubMed |
description | Acute kidney injury (AKI) results in microvascular damage that if not normally repaired, may lead to fibrosis. The Id1 and 3 proteins have a critical role in promoting angiogenesis during development, tumor growth and wound repair by functioning as dominant negative regulators of bHLH transcription factors. The goal of this study was to determine if Id proteins regulate microvascular repair and remodeling and if increased Id1 expression results in decreased capillary loss following AKI. The effect of changes in Id expression in vivo was examined using Id1−/−, Id3RFP/+ (Id1/Id3 KO) and Tek (Tie2)-rtTA, TRE-lacz/TRE Id1 (TRE Id1) mice with doxycycline inducible endothelial Id1 and β-galactosidase expression. Id1 and 3 were co-localized in endothelial cells in normal adult kidneys and protein levels were increased at day 3 following ischemia-reperfusion injury (IRI) and contralateral nephrectomy. Id1/Id3 KO mice had decreased baseline capillary density and pericyte coverage and increased tubular damage following IRI but decreased interstitial cell proliferation and fibrosis compared with WT littermates. No compensatory increase in kidney size occurred in KO mice resulting in increased creatinine compared with WT and TRE Id1 mice. TRE Id1 mice had no capillary rarefaction within 1 week following IRI in comparison with WT littermates. TRE Id1 mice had increased proliferation of PDGFRβ positive interstitial cells and medullary collagen deposition and developed capillary rarefaction and albuminuria at later time points. These differences were associated with increased Angiopoietin 1 (Ang1) and decreased Ang2 expression in TRE Id1 mice. Examination of gene expression in microvascular cells isolated from WT, Id1/Id3 KO and TRE Id1 mice showed increased Ang1 and αSMA in Id1 overexpressing cells and decreased pericyte markers in cells from KO mice. These results suggest that increased Id levels following AKI result in microvascular remodeling associated with increased fibrosis. |
format | Online Article Text |
id | pubmed-3917915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39179152014-02-10 Id Proteins Regulate Capillary Repair and Perivascular Cell Proliferation following Ischemia-Reperfusion Injury Lee, David Shenoy, Shantheri Nigatu, Yezina Plotkin, Matt PLoS One Research Article Acute kidney injury (AKI) results in microvascular damage that if not normally repaired, may lead to fibrosis. The Id1 and 3 proteins have a critical role in promoting angiogenesis during development, tumor growth and wound repair by functioning as dominant negative regulators of bHLH transcription factors. The goal of this study was to determine if Id proteins regulate microvascular repair and remodeling and if increased Id1 expression results in decreased capillary loss following AKI. The effect of changes in Id expression in vivo was examined using Id1−/−, Id3RFP/+ (Id1/Id3 KO) and Tek (Tie2)-rtTA, TRE-lacz/TRE Id1 (TRE Id1) mice with doxycycline inducible endothelial Id1 and β-galactosidase expression. Id1 and 3 were co-localized in endothelial cells in normal adult kidneys and protein levels were increased at day 3 following ischemia-reperfusion injury (IRI) and contralateral nephrectomy. Id1/Id3 KO mice had decreased baseline capillary density and pericyte coverage and increased tubular damage following IRI but decreased interstitial cell proliferation and fibrosis compared with WT littermates. No compensatory increase in kidney size occurred in KO mice resulting in increased creatinine compared with WT and TRE Id1 mice. TRE Id1 mice had no capillary rarefaction within 1 week following IRI in comparison with WT littermates. TRE Id1 mice had increased proliferation of PDGFRβ positive interstitial cells and medullary collagen deposition and developed capillary rarefaction and albuminuria at later time points. These differences were associated with increased Angiopoietin 1 (Ang1) and decreased Ang2 expression in TRE Id1 mice. Examination of gene expression in microvascular cells isolated from WT, Id1/Id3 KO and TRE Id1 mice showed increased Ang1 and αSMA in Id1 overexpressing cells and decreased pericyte markers in cells from KO mice. These results suggest that increased Id levels following AKI result in microvascular remodeling associated with increased fibrosis. Public Library of Science 2014-02-07 /pmc/articles/PMC3917915/ /pubmed/24516656 http://dx.doi.org/10.1371/journal.pone.0088417 Text en © 2014 Lee 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lee, David Shenoy, Shantheri Nigatu, Yezina Plotkin, Matt Id Proteins Regulate Capillary Repair and Perivascular Cell Proliferation following Ischemia-Reperfusion Injury |
title | Id Proteins Regulate Capillary Repair and Perivascular Cell Proliferation following Ischemia-Reperfusion Injury |
title_full | Id Proteins Regulate Capillary Repair and Perivascular Cell Proliferation following Ischemia-Reperfusion Injury |
title_fullStr | Id Proteins Regulate Capillary Repair and Perivascular Cell Proliferation following Ischemia-Reperfusion Injury |
title_full_unstemmed | Id Proteins Regulate Capillary Repair and Perivascular Cell Proliferation following Ischemia-Reperfusion Injury |
title_short | Id Proteins Regulate Capillary Repair and Perivascular Cell Proliferation following Ischemia-Reperfusion Injury |
title_sort | id proteins regulate capillary repair and perivascular cell proliferation following ischemia-reperfusion injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917915/ https://www.ncbi.nlm.nih.gov/pubmed/24516656 http://dx.doi.org/10.1371/journal.pone.0088417 |
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