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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,...

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Autores principales: Ikeda, Yasumasa, Ozono, Iori, Tajima, Soichiro, Imao, Mizuki, Horinouchi, Yuya, Izawa-Ishizawa, Yuki, Kihira, Yoshitaka, Miyamoto, Licht, Ishizawa, Keisuke, Tsuchiya, Koichiro, Tamaki, Toshiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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.
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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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