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Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts
Autophagy (cellular self-consumption) is a crucial adaptation mechanism during cellular stress conditions. This study aimed to examine how this important process is regulated in human periodontal ligament (PDL) fibroblasts by mechanical and inflammatory stress conditions and whether the mammalian ta...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763506/ https://www.ncbi.nlm.nih.gov/pubmed/33322510 http://dx.doi.org/10.3390/ijms21249446 |
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author | Blawat, Kim Mayr, Alexandra Hardt, Miriam Kirschneck, Christian Nokhbehsaim, Marjan Behl, Christian Deschner, James Jäger, Andreas Memmert, Svenja |
author_facet | Blawat, Kim Mayr, Alexandra Hardt, Miriam Kirschneck, Christian Nokhbehsaim, Marjan Behl, Christian Deschner, James Jäger, Andreas Memmert, Svenja |
author_sort | Blawat, Kim |
collection | PubMed |
description | Autophagy (cellular self-consumption) is a crucial adaptation mechanism during cellular stress conditions. This study aimed to examine how this important process is regulated in human periodontal ligament (PDL) fibroblasts by mechanical and inflammatory stress conditions and whether the mammalian target of rapamycin (mTOR) signaling pathway is involved. Autophagy was quantified by flow cytometry. Qualitative protein phosphorylation profiling of the mTOR pathway was carried out. Effects of mTOR regulation were assessed by quantification of important synthesis product collagen 1, cell proliferation and cell death with real-time PCR and flow cytometry. Autophagy as a response to mechanical or inflammatory treatment in PDL fibroblasts was dose and time dependent. In general, autophagy was induced by stress stimulation. Phosphorylation analysis of mTOR showed regulatory influences of mechanical and inflammatory stimulation on crucial target proteins. Regulation of mTOR was also detectable via changes in protein synthesis and cell proliferation. Physiological pressure had cell-protective effects (p = 0.025), whereas overload increased cell death (p = 0.003), which was also promoted in long-term inflammatory treatment (p < 0.001). Our data provide novel insights about autophagy regulation by mechanical and inflammatory stress conditions in human PDL fibroblasts. Our results suggest some involvement of the mTOR pathway in autophagy and cell fate regulation under the named conditions. |
format | Online Article Text |
id | pubmed-7763506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77635062020-12-27 Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts Blawat, Kim Mayr, Alexandra Hardt, Miriam Kirschneck, Christian Nokhbehsaim, Marjan Behl, Christian Deschner, James Jäger, Andreas Memmert, Svenja Int J Mol Sci Article Autophagy (cellular self-consumption) is a crucial adaptation mechanism during cellular stress conditions. This study aimed to examine how this important process is regulated in human periodontal ligament (PDL) fibroblasts by mechanical and inflammatory stress conditions and whether the mammalian target of rapamycin (mTOR) signaling pathway is involved. Autophagy was quantified by flow cytometry. Qualitative protein phosphorylation profiling of the mTOR pathway was carried out. Effects of mTOR regulation were assessed by quantification of important synthesis product collagen 1, cell proliferation and cell death with real-time PCR and flow cytometry. Autophagy as a response to mechanical or inflammatory treatment in PDL fibroblasts was dose and time dependent. In general, autophagy was induced by stress stimulation. Phosphorylation analysis of mTOR showed regulatory influences of mechanical and inflammatory stimulation on crucial target proteins. Regulation of mTOR was also detectable via changes in protein synthesis and cell proliferation. Physiological pressure had cell-protective effects (p = 0.025), whereas overload increased cell death (p = 0.003), which was also promoted in long-term inflammatory treatment (p < 0.001). Our data provide novel insights about autophagy regulation by mechanical and inflammatory stress conditions in human PDL fibroblasts. Our results suggest some involvement of the mTOR pathway in autophagy and cell fate regulation under the named conditions. MDPI 2020-12-11 /pmc/articles/PMC7763506/ /pubmed/33322510 http://dx.doi.org/10.3390/ijms21249446 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Blawat, Kim Mayr, Alexandra Hardt, Miriam Kirschneck, Christian Nokhbehsaim, Marjan Behl, Christian Deschner, James Jäger, Andreas Memmert, Svenja Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts |
title | Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts |
title_full | Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts |
title_fullStr | Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts |
title_full_unstemmed | Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts |
title_short | Regulation of Autophagic Signaling by Mechanical Loading and Inflammation in Human PDL Fibroblasts |
title_sort | regulation of autophagic signaling by mechanical loading and inflammation in human pdl fibroblasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763506/ https://www.ncbi.nlm.nih.gov/pubmed/33322510 http://dx.doi.org/10.3390/ijms21249446 |
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