Cargando…
Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis
Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibit...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052035/ https://www.ncbi.nlm.nih.gov/pubmed/30022146 http://dx.doi.org/10.1038/s41598-018-29008-2 |
_version_ | 1783340592173940736 |
---|---|
author | Horinouchi, Yuya Ikeda, Yasumasa Fukushima, Keijo Imanishi, Masaki Hamano, Hirofumi Izawa-Ishizawa, Yuki Zamami, Yoshito Takechi, Kenshi Miyamoto, Licht Fujino, Hiromichi Ishizawa, Keisuke Tsuchiya, Koichiro Tamaki, Toshiaki |
author_facet | Horinouchi, Yuya Ikeda, Yasumasa Fukushima, Keijo Imanishi, Masaki Hamano, Hirofumi Izawa-Ishizawa, Yuki Zamami, Yoshito Takechi, Kenshi Miyamoto, Licht Fujino, Hiromichi Ishizawa, Keisuke Tsuchiya, Koichiro Tamaki, Toshiaki |
author_sort | Horinouchi, Yuya |
collection | PubMed |
description | Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis. |
format | Online Article Text |
id | pubmed-6052035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60520352018-07-23 Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis Horinouchi, Yuya Ikeda, Yasumasa Fukushima, Keijo Imanishi, Masaki Hamano, Hirofumi Izawa-Ishizawa, Yuki Zamami, Yoshito Takechi, Kenshi Miyamoto, Licht Fujino, Hiromichi Ishizawa, Keisuke Tsuchiya, Koichiro Tamaki, Toshiaki Sci Rep Article Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis. Nature Publishing Group UK 2018-07-18 /pmc/articles/PMC6052035/ /pubmed/30022146 http://dx.doi.org/10.1038/s41598-018-29008-2 Text en © The Author(s) 2018 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 Horinouchi, Yuya Ikeda, Yasumasa Fukushima, Keijo Imanishi, Masaki Hamano, Hirofumi Izawa-Ishizawa, Yuki Zamami, Yoshito Takechi, Kenshi Miyamoto, Licht Fujino, Hiromichi Ishizawa, Keisuke Tsuchiya, Koichiro Tamaki, Toshiaki Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis |
title | Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis |
title_full | Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis |
title_fullStr | Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis |
title_full_unstemmed | Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis |
title_short | Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis |
title_sort | renoprotective effects of a factor xa inhibitor: fusion of basic research and a database analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052035/ https://www.ncbi.nlm.nih.gov/pubmed/30022146 http://dx.doi.org/10.1038/s41598-018-29008-2 |
work_keys_str_mv | AT horinouchiyuya renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT ikedayasumasa renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT fukushimakeijo renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT imanishimasaki renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT hamanohirofumi renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT izawaishizawayuki renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT zamamiyoshito renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT takechikenshi renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT miyamotolicht renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT fujinohiromichi renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT ishizawakeisuke renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT tsuchiyakoichiro renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis AT tamakitoshiaki renoprotectiveeffectsofafactorxainhibitorfusionofbasicresearchandadatabaseanalysis |