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Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia
Progranulin (PGRN) plays a crucial role in diverse biological processes, including cell proliferation and embryonic development. PGRN can be cleaved by neutrophil elastase to release granulin (GRN). PGRN has been found to inhibit inflammation. Whereas, GRN plays a role as a pro-inflammatory factor....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829276/ https://www.ncbi.nlm.nih.gov/pubmed/31640144 http://dx.doi.org/10.3390/ijms20205210 |
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author | Horinokita, Ichiro Hayashi, Hideki Oteki, Rika Mizumura, Risa Yamaguchi, Tatsuaki Usui, Akane Yuan, Bo Takagi, Norio |
author_facet | Horinokita, Ichiro Hayashi, Hideki Oteki, Rika Mizumura, Risa Yamaguchi, Tatsuaki Usui, Akane Yuan, Bo Takagi, Norio |
author_sort | Horinokita, Ichiro |
collection | PubMed |
description | Progranulin (PGRN) plays a crucial role in diverse biological processes, including cell proliferation and embryonic development. PGRN can be cleaved by neutrophil elastase to release granulin (GRN). PGRN has been found to inhibit inflammation. Whereas, GRN plays a role as a pro-inflammatory factor. However, the pathophysiological roles of PGRN and GRN, at early stages after cerebral ischemia, have not yet been fully understood. The aim of this study was to obtain further insight into the pathologic roles of PGRN and GRN. We demonstrated that the amount of PGRN was significantly increased in microglial cells after cerebral ischemia in rats and that neutrophil elastase activity was also increased at an early stage after cerebral ischemia, resulting in the production of GRN. The inhibition of neutrophil elastase activity suppressed PGRN cleavage and GRN production, as well as the increase in pro-inflammatory cytokines, after cerebral ischemia. The administration of an elastase inhibitor decreased the number of injured cells and improved the neurological deficits test scores. Our findings suggest that an increase in the activity of elastase to cleave PGRN, and to produce GRN, was involved in an inflammatory response at the early stages after cerebral ischemia, and that inhibition of elastase activity could suppress the progression of cerebral ischemic injury. |
format | Online Article Text |
id | pubmed-6829276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68292762019-11-18 Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia Horinokita, Ichiro Hayashi, Hideki Oteki, Rika Mizumura, Risa Yamaguchi, Tatsuaki Usui, Akane Yuan, Bo Takagi, Norio Int J Mol Sci Article Progranulin (PGRN) plays a crucial role in diverse biological processes, including cell proliferation and embryonic development. PGRN can be cleaved by neutrophil elastase to release granulin (GRN). PGRN has been found to inhibit inflammation. Whereas, GRN plays a role as a pro-inflammatory factor. However, the pathophysiological roles of PGRN and GRN, at early stages after cerebral ischemia, have not yet been fully understood. The aim of this study was to obtain further insight into the pathologic roles of PGRN and GRN. We demonstrated that the amount of PGRN was significantly increased in microglial cells after cerebral ischemia in rats and that neutrophil elastase activity was also increased at an early stage after cerebral ischemia, resulting in the production of GRN. The inhibition of neutrophil elastase activity suppressed PGRN cleavage and GRN production, as well as the increase in pro-inflammatory cytokines, after cerebral ischemia. The administration of an elastase inhibitor decreased the number of injured cells and improved the neurological deficits test scores. Our findings suggest that an increase in the activity of elastase to cleave PGRN, and to produce GRN, was involved in an inflammatory response at the early stages after cerebral ischemia, and that inhibition of elastase activity could suppress the progression of cerebral ischemic injury. MDPI 2019-10-21 /pmc/articles/PMC6829276/ /pubmed/31640144 http://dx.doi.org/10.3390/ijms20205210 Text en © 2019 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 Horinokita, Ichiro Hayashi, Hideki Oteki, Rika Mizumura, Risa Yamaguchi, Tatsuaki Usui, Akane Yuan, Bo Takagi, Norio Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia |
title | Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia |
title_full | Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia |
title_fullStr | Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia |
title_full_unstemmed | Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia |
title_short | Involvement of Progranulin and Granulin Expression in Inflammatory Responses after Cerebral Ischemia |
title_sort | involvement of progranulin and granulin expression in inflammatory responses after cerebral ischemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829276/ https://www.ncbi.nlm.nih.gov/pubmed/31640144 http://dx.doi.org/10.3390/ijms20205210 |
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