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Autophagy induction and PDGFR-β knockdown by siRNA-encapsulated nanoparticles reduce chlamydia trachomatis infection

C. trachomatis is the most common sexually transmitted bacterial infection in the world. Although the infection can be easily controlled by the use of antibiotics, several reports of clinical isolates that are resistant to antibiotics have prompted us to search for alternative strategies to manage t...

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Autores principales: Yang, Sidi, Traore, Yannick, Jimenez, Celine, Ho, Emmanuel A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361950/
https://www.ncbi.nlm.nih.gov/pubmed/30718536
http://dx.doi.org/10.1038/s41598-018-36601-y
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author Yang, Sidi
Traore, Yannick
Jimenez, Celine
Ho, Emmanuel A.
author_facet Yang, Sidi
Traore, Yannick
Jimenez, Celine
Ho, Emmanuel A.
author_sort Yang, Sidi
collection PubMed
description C. trachomatis is the most common sexually transmitted bacterial infection in the world. Although the infection can be easily controlled by the use of antibiotics, several reports of clinical isolates that are resistant to antibiotics have prompted us to search for alternative strategies to manage this disease. In this paper, we developed a nanoparticle formulation (PDGFR-β siRNA-PEI-PLGA-PEG NP) that can simultaneously induce autophagy in human cells and knock down PDGFR-β gene expression, an important surface binding protein for C. trachomatis, as a strategy to reduce vaginal infection of C. trachomatis. PDGFR-β siRNA-PEI-PLGA-PEG NP significantly induced autophagy in human vaginal epithelial cells (VK2/E6E7) 48 hr post treatment by improving autophagic degradation activity without causing inflammation, apoptosis or any decrease in cell viability. Beclin-1, VPS34 (markers for initiation stage of autophagy), UVRAG, TECPR-1 (markers for degradation stage of autophagy) were found to be significantly upregulated after treatment with PDGFR-β siRNA-PEI-PLGA-PEG NP. Furthermore, PDGFR-β siRNA-PEI-PLGA-PEG NP decreased PDGFR-β mRNA expression by 50% and protein expression by 43% in VK2/E6E7 cells 48 hr post treatment. Treatment of cells with PDGFR-β siRNA-PEI-PLGA-PEG NP significantly decreased the intracellular C. trachomatis and extracellular release of C. trachomatis by approximately 65% and 67%, respectively, in vitro through augmenting autophagic degradation pathways and reducing bacterial binding simultaneously.
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spelling pubmed-63619502019-02-06 Autophagy induction and PDGFR-β knockdown by siRNA-encapsulated nanoparticles reduce chlamydia trachomatis infection Yang, Sidi Traore, Yannick Jimenez, Celine Ho, Emmanuel A. Sci Rep Article C. trachomatis is the most common sexually transmitted bacterial infection in the world. Although the infection can be easily controlled by the use of antibiotics, several reports of clinical isolates that are resistant to antibiotics have prompted us to search for alternative strategies to manage this disease. In this paper, we developed a nanoparticle formulation (PDGFR-β siRNA-PEI-PLGA-PEG NP) that can simultaneously induce autophagy in human cells and knock down PDGFR-β gene expression, an important surface binding protein for C. trachomatis, as a strategy to reduce vaginal infection of C. trachomatis. PDGFR-β siRNA-PEI-PLGA-PEG NP significantly induced autophagy in human vaginal epithelial cells (VK2/E6E7) 48 hr post treatment by improving autophagic degradation activity without causing inflammation, apoptosis or any decrease in cell viability. Beclin-1, VPS34 (markers for initiation stage of autophagy), UVRAG, TECPR-1 (markers for degradation stage of autophagy) were found to be significantly upregulated after treatment with PDGFR-β siRNA-PEI-PLGA-PEG NP. Furthermore, PDGFR-β siRNA-PEI-PLGA-PEG NP decreased PDGFR-β mRNA expression by 50% and protein expression by 43% in VK2/E6E7 cells 48 hr post treatment. Treatment of cells with PDGFR-β siRNA-PEI-PLGA-PEG NP significantly decreased the intracellular C. trachomatis and extracellular release of C. trachomatis by approximately 65% and 67%, respectively, in vitro through augmenting autophagic degradation pathways and reducing bacterial binding simultaneously. Nature Publishing Group UK 2019-02-04 /pmc/articles/PMC6361950/ /pubmed/30718536 http://dx.doi.org/10.1038/s41598-018-36601-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yang, Sidi
Traore, Yannick
Jimenez, Celine
Ho, Emmanuel A.
Autophagy induction and PDGFR-β knockdown by siRNA-encapsulated nanoparticles reduce chlamydia trachomatis infection
title Autophagy induction and PDGFR-β knockdown by siRNA-encapsulated nanoparticles reduce chlamydia trachomatis infection
title_full Autophagy induction and PDGFR-β knockdown by siRNA-encapsulated nanoparticles reduce chlamydia trachomatis infection
title_fullStr Autophagy induction and PDGFR-β knockdown by siRNA-encapsulated nanoparticles reduce chlamydia trachomatis infection
title_full_unstemmed Autophagy induction and PDGFR-β knockdown by siRNA-encapsulated nanoparticles reduce chlamydia trachomatis infection
title_short Autophagy induction and PDGFR-β knockdown by siRNA-encapsulated nanoparticles reduce chlamydia trachomatis infection
title_sort autophagy induction and pdgfr-β knockdown by sirna-encapsulated nanoparticles reduce chlamydia trachomatis infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361950/
https://www.ncbi.nlm.nih.gov/pubmed/30718536
http://dx.doi.org/10.1038/s41598-018-36601-y
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