Back to Search
Start Over
Macrophage and epithelial cell H-ferritin expression regulates renal inflammation
- Source :
- Kidney international, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Publication Year :
- 2015
- Publisher :
- Elsevier, 2015.
-
Abstract
- The deposited article is a post-print version (author's manuscript from PMC). This publication hasn't any creative commons license associated. The deposited article version contains attached the supplementary materials within the pdf. 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. NIH grants: (R01 DK5960, R01 DK5960, P30 DK079337, R01 DK083390); Fundação para a Ciência e Tecnologia grants: (PTDC/SAU-TOX/116627/2010, HMSP-ICT/0022/2010); European Union grant: (ERC-2011-AdG. 294709 DAMAGECONTROL); AHA grant: (11POST7600074). info:eu-repo/semantics/publishedVersion
- Subjects :
- Male
Pathology
Gene Expression
Kidney
Kidney Tubules, Proximal
Mice
Fibrosis
Macrophage
Myeloid Cells
Cells, Cultured
Chemokine CCL2
Nephritis
Orvostudományok
Interleukin-10
Interleukin 10
medicine.anatomical_structure
acute kidney injury
Nephrology
medicine.symptom
Ureteral Obstruction
Macrophage colony-stimulating factor
medicine.medical_specialty
macrophage polarization
Macrophage polarization
Inflammation
Mice, Transgenic
Biology
Klinikai orvostudományok
Acute kidney injury
Ferritin
Article
Proinflammatory cytokine
medicine
Animals
RNA, Messenger
Interleukin-6
Macrophage Colony-Stimulating Factor
Macrophages
fibrosis
Epithelial Cells
Macrophage Activation
medicine.disease
Molecular biology
Mice, Inbred C57BL
Disease Models, Animal
inflammation
Apoferritins
Heme Oxygenase-1
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Kidney international, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Accession number :
- edsair.doi.dedup.....e0c23cb5522d9b3e1896e5c9f2bc624b