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Iron Chelation by Deferoxamine Prevents Renal Interstitial Fibrosis in Mice with Unilateral Ureteral Obstruction
Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929716/ https://www.ncbi.nlm.nih.gov/pubmed/24586712 http://dx.doi.org/10.1371/journal.pone.0089355 |
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author | Ikeda, Yasumasa Ozono, Iori Tajima, Soichiro Imao, Mizuki Horinouchi, Yuya Izawa-Ishizawa, Yuki Kihira, Yoshitaka Miyamoto, Licht Ishizawa, Keisuke Tsuchiya, Koichiro Tamaki, Toshiaki |
author_facet | Ikeda, Yasumasa Ozono, Iori Tajima, Soichiro Imao, Mizuki Horinouchi, Yuya Izawa-Ishizawa, Yuki Kihira, Yoshitaka Miyamoto, Licht Ishizawa, Keisuke Tsuchiya, Koichiro Tamaki, Toshiaki |
author_sort | Ikeda, Yasumasa |
collection | PubMed |
description | Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22(phox) expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses. |
format | Online Article Text |
id | pubmed-3929716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39297162014-02-25 Iron Chelation by Deferoxamine Prevents Renal Interstitial Fibrosis in Mice with Unilateral Ureteral Obstruction Ikeda, Yasumasa Ozono, Iori Tajima, Soichiro Imao, Mizuki Horinouchi, Yuya Izawa-Ishizawa, Yuki Kihira, Yoshitaka Miyamoto, Licht Ishizawa, Keisuke Tsuchiya, Koichiro Tamaki, Toshiaki PLoS One Research Article Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22(phox) expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses. Public Library of Science 2014-02-19 /pmc/articles/PMC3929716/ /pubmed/24586712 http://dx.doi.org/10.1371/journal.pone.0089355 Text en © 2014 Ikeda et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ikeda, Yasumasa Ozono, Iori Tajima, Soichiro Imao, Mizuki Horinouchi, Yuya Izawa-Ishizawa, Yuki Kihira, Yoshitaka Miyamoto, Licht Ishizawa, Keisuke Tsuchiya, Koichiro Tamaki, Toshiaki Iron Chelation by Deferoxamine Prevents Renal Interstitial Fibrosis in Mice with Unilateral Ureteral Obstruction |
title | Iron Chelation by Deferoxamine Prevents Renal Interstitial Fibrosis in Mice with Unilateral Ureteral Obstruction |
title_full | Iron Chelation by Deferoxamine Prevents Renal Interstitial Fibrosis in Mice with Unilateral Ureteral Obstruction |
title_fullStr | Iron Chelation by Deferoxamine Prevents Renal Interstitial Fibrosis in Mice with Unilateral Ureteral Obstruction |
title_full_unstemmed | Iron Chelation by Deferoxamine Prevents Renal Interstitial Fibrosis in Mice with Unilateral Ureteral Obstruction |
title_short | Iron Chelation by Deferoxamine Prevents Renal Interstitial Fibrosis in Mice with Unilateral Ureteral Obstruction |
title_sort | iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929716/ https://www.ncbi.nlm.nih.gov/pubmed/24586712 http://dx.doi.org/10.1371/journal.pone.0089355 |
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