Cargando…
The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system
Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that controls the cellular response to oxidative stress and possesses DNA-repair functions. It has important roles in the progression and outcomes of various diseases; however, its function and therapeutic prospects with respec...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534557/ https://www.ncbi.nlm.nih.gov/pubmed/31127150 http://dx.doi.org/10.1038/s41598-019-44241-z |
_version_ | 1783421432470962176 |
---|---|
author | Maruyama, Keisuke Nakagawa, Naoki Aonuma, Tatsuya Saito, Yukihiro Hayasaka, Taiki Kano, Kohei Horiuchi, Kiwamu Takehara, Naofumi Kawabe, Jun-ichi Hasebe, Naoyuki |
author_facet | Maruyama, Keisuke Nakagawa, Naoki Aonuma, Tatsuya Saito, Yukihiro Hayasaka, Taiki Kano, Kohei Horiuchi, Kiwamu Takehara, Naofumi Kawabe, Jun-ichi Hasebe, Naoyuki |
author_sort | Maruyama, Keisuke |
collection | PubMed |
description | Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that controls the cellular response to oxidative stress and possesses DNA-repair functions. It has important roles in the progression and outcomes of various diseases; however, its function and therapeutic prospects with respect to kidney injury are unknown. To study this, we activated APE1 during kidney injury by constructing an expression vector (pCAG-APE1), using an EGFP expression plasmid (pCAG-EGFP) as a control. We performed unilateral ureteral obstruction (UUO) as a model of tubulointerstitial fibrosis on ICR mice before each vector was administrated via retrograde renal vein injection. In this model, pCAG-APE1 injection did not produce any adverse effects and significantly reduced histological end points including fibrosis, inflammation, tubular injury, and oxidative stress, as compared to those parameters after pCAG-EGFP injection. qPCR analysis showed significantly lower expression of Casp3 and inflammation-related genes in pCAG-APE1-injected animals compared to those in pCAG-EGFP-injected UUO kidneys. RNA-Seq analyses showed that the major transcriptional changes in pCAG-APE1-injected UUO kidneys were related to immune system processes, metabolic processes, catalytic activity, and apoptosis, leading to normal kidney repair. Therefore, APE1 suppressed renal fibrosis, not only via antioxidant and DNA-repair functions, but also partly by modulating the immune system through multiple pathways including Il6, Tnf, and chemokine families. Thus, therapeutic APE1 modulation might be beneficial for the treatment of renal diseases. |
format | Online Article Text |
id | pubmed-6534557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65345572019-06-03 The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system Maruyama, Keisuke Nakagawa, Naoki Aonuma, Tatsuya Saito, Yukihiro Hayasaka, Taiki Kano, Kohei Horiuchi, Kiwamu Takehara, Naofumi Kawabe, Jun-ichi Hasebe, Naoyuki Sci Rep Article Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that controls the cellular response to oxidative stress and possesses DNA-repair functions. It has important roles in the progression and outcomes of various diseases; however, its function and therapeutic prospects with respect to kidney injury are unknown. To study this, we activated APE1 during kidney injury by constructing an expression vector (pCAG-APE1), using an EGFP expression plasmid (pCAG-EGFP) as a control. We performed unilateral ureteral obstruction (UUO) as a model of tubulointerstitial fibrosis on ICR mice before each vector was administrated via retrograde renal vein injection. In this model, pCAG-APE1 injection did not produce any adverse effects and significantly reduced histological end points including fibrosis, inflammation, tubular injury, and oxidative stress, as compared to those parameters after pCAG-EGFP injection. qPCR analysis showed significantly lower expression of Casp3 and inflammation-related genes in pCAG-APE1-injected animals compared to those in pCAG-EGFP-injected UUO kidneys. RNA-Seq analyses showed that the major transcriptional changes in pCAG-APE1-injected UUO kidneys were related to immune system processes, metabolic processes, catalytic activity, and apoptosis, leading to normal kidney repair. Therefore, APE1 suppressed renal fibrosis, not only via antioxidant and DNA-repair functions, but also partly by modulating the immune system through multiple pathways including Il6, Tnf, and chemokine families. Thus, therapeutic APE1 modulation might be beneficial for the treatment of renal diseases. Nature Publishing Group UK 2019-05-24 /pmc/articles/PMC6534557/ /pubmed/31127150 http://dx.doi.org/10.1038/s41598-019-44241-z 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 Maruyama, Keisuke Nakagawa, Naoki Aonuma, Tatsuya Saito, Yukihiro Hayasaka, Taiki Kano, Kohei Horiuchi, Kiwamu Takehara, Naofumi Kawabe, Jun-ichi Hasebe, Naoyuki The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system |
title | The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system |
title_full | The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system |
title_fullStr | The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system |
title_full_unstemmed | The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system |
title_short | The antioxidant and DNA-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system |
title_sort | antioxidant and dna-repair enzyme apurinic/apyrimidinic endonuclease 1 limits the development of tubulointerstitial fibrosis partly by modulating the immune system |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534557/ https://www.ncbi.nlm.nih.gov/pubmed/31127150 http://dx.doi.org/10.1038/s41598-019-44241-z |
work_keys_str_mv | AT maruyamakeisuke theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT nakagawanaoki theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT aonumatatsuya theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT saitoyukihiro theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT hayasakataiki theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT kanokohei theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT horiuchikiwamu theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT takeharanaofumi theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT kawabejunichi theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT hasebenaoyuki theantioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT maruyamakeisuke antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT nakagawanaoki antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT aonumatatsuya antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT saitoyukihiro antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT hayasakataiki antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT kanokohei antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT horiuchikiwamu antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT takeharanaofumi antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT kawabejunichi antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem AT hasebenaoyuki antioxidantanddnarepairenzymeapurinicapyrimidinicendonuclease1limitsthedevelopmentoftubulointerstitialfibrosispartlybymodulatingtheimmunesystem |