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Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis

BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS), most commonly seen during the organ dysfunction remains unsatisfied. Presently, the stem/progenitor cell-based endogenous repair has been aroused attention enormously. This report investigated the effects of retinoic acid (RA)...

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Autores principales: Yang, Ce, Yang, Xuetao, Du, Juan, Wang, Haiyan, Li, Haisheng, Zeng, Ling, Gu, Wei, Jiang, Jianxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642746/
https://www.ncbi.nlm.nih.gov/pubmed/26561298
http://dx.doi.org/10.1186/s12931-015-0300-9
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author Yang, Ce
Yang, Xuetao
Du, Juan
Wang, Haiyan
Li, Haisheng
Zeng, Ling
Gu, Wei
Jiang, Jianxin
author_facet Yang, Ce
Yang, Xuetao
Du, Juan
Wang, Haiyan
Li, Haisheng
Zeng, Ling
Gu, Wei
Jiang, Jianxin
author_sort Yang, Ce
collection PubMed
description BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS), most commonly seen during the organ dysfunction remains unsatisfied. Presently, the stem/progenitor cell-based endogenous repair has been aroused attention enormously. This report investigated the effects of retinoic acid (RA) plus simvastatin (SS) with respect to dynamics of lung repair cells as well as to elucidate the underlying mechanism. MATERIALS AND METHODS: The experimental Sprague–Dawley rats were divided randomly into normal control (control), sham operated (sham), ARDS, ARDS + vehicle and ARDS + RA + SS groups. ARDS was reproduced through hemorrhagic shock/resuscitation (shock) and subsequent intratracheal LPS (4.5 mg/kg, Escherichia coli serotype O55: B5) injection. The rats were treated by intragastric administration of RA (2 mg/kg/day) and SS (2 mg/kg/day) for 5 days in the ARDS + RA + SS group. Seven days after the first RA-SS injection, a right lower lobe of lung was sampled for histological analysis concerning systemic uniform random sampling method. Immunohistochemistry of inflation-fixed lungs for alveolar type 1 (AT1), alveolar type 2 (AT2) and Clara cells was measured by AQP5, Pro-SPC and CCSP staining respectively. The alveolar cell proliferation and apoptosis were analyzed with Ki67 staining and terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling (TUNEL) method. Meanwhile, the alveolar cell numerical and surface density (alveolar cells, AT1, AT2, Clara, proliferating and apoptotic cells) were evaluated by stereology. RESULTS: RA-SS compound exerted anti-inflammatory and pro-repairing effects on respiratory tracts in ARDS induced by hemorrhagic-endotoxin shock. The numerical density and surface density of alveolar cells, AT1 cell fraction, and numerical density of AT2 and Clara cells were significantly increased after treatment with RA-SS compound in ARDS. Concurrently, the Ki67+ alveolar cells were obviously increased while the TUNEL+ alveolar cells were reduced, which was correlated with the attenuation of inflammatory injury and functional repair in injured lung tissues. CONCLUSIONS: Our data convincingly indicated that the prophylactic and therapeutic treatment of RA plus SS had obvious beneficial effect on the remodeling/regeneration of injured pulmonary tissues, suggesting that the underlying mechanisms are related to the re-balance between regeneration and apoptosis in lung stem/progenitor cells.
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spelling pubmed-46427462015-11-13 Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis Yang, Ce Yang, Xuetao Du, Juan Wang, Haiyan Li, Haisheng Zeng, Ling Gu, Wei Jiang, Jianxin Respir Res Research BACKGROUND: The treatment of acute respiratory distress syndrome (ARDS), most commonly seen during the organ dysfunction remains unsatisfied. Presently, the stem/progenitor cell-based endogenous repair has been aroused attention enormously. This report investigated the effects of retinoic acid (RA) plus simvastatin (SS) with respect to dynamics of lung repair cells as well as to elucidate the underlying mechanism. MATERIALS AND METHODS: The experimental Sprague–Dawley rats were divided randomly into normal control (control), sham operated (sham), ARDS, ARDS + vehicle and ARDS + RA + SS groups. ARDS was reproduced through hemorrhagic shock/resuscitation (shock) and subsequent intratracheal LPS (4.5 mg/kg, Escherichia coli serotype O55: B5) injection. The rats were treated by intragastric administration of RA (2 mg/kg/day) and SS (2 mg/kg/day) for 5 days in the ARDS + RA + SS group. Seven days after the first RA-SS injection, a right lower lobe of lung was sampled for histological analysis concerning systemic uniform random sampling method. Immunohistochemistry of inflation-fixed lungs for alveolar type 1 (AT1), alveolar type 2 (AT2) and Clara cells was measured by AQP5, Pro-SPC and CCSP staining respectively. The alveolar cell proliferation and apoptosis were analyzed with Ki67 staining and terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling (TUNEL) method. Meanwhile, the alveolar cell numerical and surface density (alveolar cells, AT1, AT2, Clara, proliferating and apoptotic cells) were evaluated by stereology. RESULTS: RA-SS compound exerted anti-inflammatory and pro-repairing effects on respiratory tracts in ARDS induced by hemorrhagic-endotoxin shock. The numerical density and surface density of alveolar cells, AT1 cell fraction, and numerical density of AT2 and Clara cells were significantly increased after treatment with RA-SS compound in ARDS. Concurrently, the Ki67+ alveolar cells were obviously increased while the TUNEL+ alveolar cells were reduced, which was correlated with the attenuation of inflammatory injury and functional repair in injured lung tissues. CONCLUSIONS: Our data convincingly indicated that the prophylactic and therapeutic treatment of RA plus SS had obvious beneficial effect on the remodeling/regeneration of injured pulmonary tissues, suggesting that the underlying mechanisms are related to the re-balance between regeneration and apoptosis in lung stem/progenitor cells. BioMed Central 2015-11-11 2015 /pmc/articles/PMC4642746/ /pubmed/26561298 http://dx.doi.org/10.1186/s12931-015-0300-9 Text en © Yang et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Yang, Ce
Yang, Xuetao
Du, Juan
Wang, Haiyan
Li, Haisheng
Zeng, Ling
Gu, Wei
Jiang, Jianxin
Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis
title Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis
title_full Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis
title_fullStr Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis
title_full_unstemmed Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis
title_short Retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis
title_sort retinoic acid promotes the endogenous repair of lung stem/progenitor cells in combined with simvastatin after acute lung injury: a stereological analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642746/
https://www.ncbi.nlm.nih.gov/pubmed/26561298
http://dx.doi.org/10.1186/s12931-015-0300-9
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