Mechanisms of HO-1 mediated attenuation of renal immune injury: a gene profiling study

Using a mouse model of immune injury directed against the renal glomerular vasculature and resembling human forms of glomerulonephritis (GN), we assessed the effect of targeted expression of the cytoprotective enzyme heme oxygenase (HO)-1. A human (h) HO-1 complementary DNAN (cDNA) sequence was targ...

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Bibliographic Details
Published in:Translational research : the journal of laboratory and clinical medicine 2011-10, Vol.158 (4), p.249-261
Main Authors: Duann, Pu, Lianos, Elias A
Format: Article
Language:English
Subjects:
Animals
Anti-Glomerular Basement Membrane Disease - enzymology
Anti-Glomerular Basement Membrane Disease - genetics
Anti-Glomerular Basement Membrane Disease - immunology
Biological and medical sciences
Disease Models, Animal
Gene Expression Profiling
General aspects
Heme Oxygenase-1 - genetics
Heme Oxygenase-1 - metabolism
Humans
Internal Medicine
Investigative techniques, diagnostic techniques (general aspects)
Kidney Glomerulus - enzymology
Kidney Glomerulus - immunology
Kidney Glomerulus - injuries
Medical sciences
Mice
Mice, Transgenic
Oligonucleotide Array Sequence Analysis
Translational Medical Research
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Summary:Using a mouse model of immune injury directed against the renal glomerular vasculature and resembling human forms of glomerulonephritis (GN), we assessed the effect of targeted expression of the cytoprotective enzyme heme oxygenase (HO)-1. A human (h) HO-1 complementary DNAN (cDNA) sequence was targeted to glomerular epithelial cells (GECs) using a GEC-specific murine nephrin promoter. Injury by administration of antibody against the glomerular basement membrane (anti-GBM) to transgenic (TG) mice with GEC-targeted hHO-1 was attenuated compared with wild-type (WT) controls. To explore changes in the expression of genes that could mediate this salutary effect, we performed gene expression profiling using a microarray analysis of RNA isolated from the renal cortex of WT or TG mice with or without anti-GBM antibody-induced injury. Significant increases in expression were detected in 9 major histocompatibility complex (MHC)-class II genes, 2 interferon-γ (IFN-γ)–inducible guanosine triphosphate (GTP)ases, and 3 genes of the ubiquitin-proteasome system. The increase in MHC-class II and proteasome gene expression in TG mice with injury was validated by real-time polymerase chain reaction (PCR) or Western blot analysis. The observations point to novel mechanisms underlying the cytoprotective effect of HO-1 in renal immune injury.
ISSN:1931-5244
1878-1810
DOI:10.1016/j.trsl.2011.06.001