title: Macrophage and epithelial cell H-ferritin expression regulates renal inflammation.
abstract: Inflammation culminating in fibrosis contributes to progressive kidney disease. Cross-talk between the tubular epithelium and interstitial cells regulates inflammation by a coordinated release of cytokines and chemokines. Here we studied the role of heme oxygenase-1 (HO-1) and the heavy subunit of ferritin (FtH) in macrophage polarization and renal inflammation. Deficiency in HO-1 was associated with increased FtH expression, accumulation of macrophages with a dysregulated polarization profile, and increased fibrosis following unilateral ureteral obstruction in mice: a model of renal inflammation and fibrosis. Macrophage polarization in vitro was predominantly dependent on FtH expression in isolated bone marrow-derived mouse monocytes. Using transgenic mice with conditional deletion of FtH in the proximal tubules (FtH(PT-/-)) or myeloid cells (FtH(LysM-/-)), we found that myeloid FtH deficiency did not affect polarization or accumulation of macrophages in the injured kidney compared with wild-type (FtH(+/+)) controls. However, tubular FtH deletion led to a marked increase in proinflammatory macrophages. Furthermore, injured kidneys from FtH(PT-/-) mice expressed significantly higher levels of inflammatory chemokines and fibrosis compared with kidneys from FtH(+/+) and FtH(LysM-/-) mice. Thus, there are differential effects of FtH in macrophages and epithelial cells, which underscore the critical role of FtH in tubular-macrophage cross-talk during kidney injury.
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Subhashini
authors: S
authors: Bolisetty
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Abolfazl
authors: A
authors: Zarjou
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Travis D
authors: TD
authors: Hull
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Amie M
authors: AM
authors: Traylor
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Anjana
authors: A
authors: Perianayagam
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Reny
authors: R
authors: Joseph
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Ahmed I
authors: AI
authors: Kamal
authors: Dipartimento Materno Infantile e Tecnologie Biomediche, University of Brescia, Brescia, Italy.
authors: Paolo
authors: P
authors: Arosio
authors: Inflammation Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors: Miguel P
authors: MP
authors: Soares
authors: 1] Department of Medicine, University of Debrecen, Debrecen, Hungary [2] MTA-DE Vascular Biology, Thrombosis and Hemostasis Research Group, Hungarian Academy of Sciences, Debrecen, Hungary.
authors: Viktoria
authors: V
authors: Jeney
authors: 1] Department of Medicine, University of Debrecen, Debrecen, Hungary [2] MTA-DE Vascular Biology, Thrombosis and Hemostasis Research Group, Hungarian Academy of Sciences, Debrecen, Hungary.
authors: Jozsef
authors: J
authors: Balla
authors: Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: James F
authors: JF
authors: George
authors: 1] Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA [2] Department of Veterans Affairs, Birmingham, Alabama, USA.
authors: Anupam
authors: A
authors: Agarwal
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism*; D005355:Fibrosis; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000172:deficiency* / Q000235:genetics; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008262:Macrophage Activation; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000378:metabolism*; D009393:Nephritis / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; D001052:Apoferritins; D051547:Heme Oxygenase-1