Proximal tubule h-ferritin mediates iron trafficking in acute kidney injury

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of Alabama at Birmingham
  • University of Brescia
  • Hungarian Academy of Sciences
  • University of Florida
  • University of Queensland
  • Swiss Federal Institute of Technology Lausanne
  • Department of Veterans Affairs

Details

Original languageEnglish (US)
Pages (from-to)4423-4434
Number of pages12
JournalJournal of Clinical Investigation
Volume123
Issue number10
StatusPublished - Oct 1 2013
Peer-reviewedYes

Abstract

Ferritin plays a central role in iron metabolism and is made of 24 subunits of 2 types: heavy chain and light chain. The ferritin heavy chain (FtH) has ferroxidase activity that is required for iron incorporation and limiting toxicity. The purpose of this study was to investigate the role of FtH in acute kidney injury (AKI) and renal iron handling by using proximal tubule-specific FtH-knockout mice (FtHPT-/- mice). FtHPT-/- mice had significant mortality, worse structural and functional renal injury, and increased levels of apoptosis in rhabdomyolysis and cisplatin-induced AKI, despite significantly higher expression of heme oxygenase-1, an antioxidant and cytoprotective enzyme. While expression of divalent metal transporter-1 was unaffected, expression of ferroportin (FPN) was significantly lower under both basal and rhabdomyolysis-induced AKI in FtHPT-/- mice. Apical localization of FPN was disrupted after AKI to a diffuse cytosolic and basolateral pattern. FtH, regardless of iron content and ferroxidase activity, induced FPN. Interestingly, urinary levels of the iron acceptor proteins neutrophil gelatinase-associated lipocalin, hemopexin, and transferrin were increased in FtHPT-/-mice after AKI. These results underscore the protective role of FtH and reveal the critical role of proximal tubule FtH in iron trafficking in AKI.

Citation formats

APA

Zarjou, A., Bolisetty, S., Joseph, R., Traylor, A., Apostolov, E. O., Arosio, P., ... Agarwal, A. (2013). Proximal tubule h-ferritin mediates iron trafficking in acute kidney injury. Journal of Clinical Investigation, 123(10), 4423-4434. https://doi.org/10.1172/JCI67867

Harvard

Zarjou, A, Bolisetty, S, Joseph, R, Traylor, A, Apostolov, EO, Arosio, P, Balla, J, Verlander, J, Darshan, D, Kuhn, LC & Agarwal, A 2013, 'Proximal tubule h-ferritin mediates iron trafficking in acute kidney injury', Journal of Clinical Investigation, vol. 123, no. 10, pp. 4423-4434. https://doi.org/10.1172/JCI67867