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The mitogen-activated protein kinase p38α regulates tubular damage in murine anti-glomerular basement membrane nephritis
- Source :
- PLoS ONE, Vol 8, Iss 2, p e56316 (2013), PLoS ONE, PLoS ONE, 8(2):e56316. PUBLIC LIBRARY SCIENCE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- p38 mitogen-activated protein kinase (MAPK) is thought to play a central role in acute and chronic inflammatory responses. Whether p38MAPK plays a pathogenic role in crescentic GN (GN) and which of its four isoforms is preferentially involved in kidney inflammation is not definitely known. We thus examined expression and activation of p38MAPK isoforms during antiglomerular basement membrane (GBM) nephritis. Therefore, p38 alpha conditional knockout mice (MxCre-p38 alpha(Delta/Delta)) were used to examine the role of p38 alpha in anti-GBM induced nephritis. Both wild type and MxCre-p38 alpha(Delta/Delta) mice developed acute renal failure over time. Histological examinations revealed a reduced monocyte influx and less tubular damage in MxCre-p38 alpha(Delta/Delta) mice, whereas glomerular crescent formation and renal fibrosis was similar. Likewise, the levels of pro-and anti-inflammatory cytokines such as TNF, IL-1 and IL-10 were similar, but IL-8 was even up-regulated in MxCre-p38 alpha(Delta/Delta) mice. In contrast, we could detect strong down-regulation of chemotactic cytokines such as CCL-2, -5 and -7, in the kidneys of MxCre-p38 alpha(Delta/Delta) mice. In conclusion, p38 alpha is the primary p38MAPK isoform expressed in anti-GBM nephritis and selectively affects inflammatory cell influx and tubular damage. Full protection from nephritis is however not achieved as renal failure and structural damage still occurs.
- Subjects :
- Pathology
Mouse
RENAL INJURY
Kidney Glomerulus
CYTOSKELETON
Signal transduction
urologic and male genital diseases
Biochemistry
p38 Mitogen-Activated Protein Kinases
ANGIOGENESIS
Mice
Molecular cell biology
Glomerulonephritis
Leukocytes
Animal Management
Mice, Knockout
Multidisciplinary
Enzyme Classes
Podocytes
Glomerular basement membrane
Signaling cascades
LOCALIZATION
Agriculture
Animal Models
Enzymes
DIFFERENTIATION
medicine.anatomical_structure
Kidney Tubules
Nephrology
Cytokines
Medicine
Tumor necrosis factor alpha
medicine.symptom
Inflammation Mediators
CRESCENTIC GLOMERULONEPHRITIS
Nephritis
Transgenic Animals
Research Article
Vasculitis
medicine.medical_specialty
MAPK signaling cascades
Phosphorylases
Medizinische Fakultät -ohne weitere Spezifikation
p38 mitogen-activated protein kinases
Science
Inflammation
Biology
Model Organisms
INFLAMMATION
Rheumatology
medicine
Renal fibrosis
Animals
ddc:610
Protein kinase A
Autoantibodies
urogenital system
SELECTIVE INHIBITOR
medicine.disease
Molecular biology
Enzyme Activation
Disease Models, Animal
Gene Expression Regulation
P38 MAP KINASE
CELLS
Gene Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....3fc2d22036924204afeecd9b6d56d299