Stem Cell Factor Expression after Renal Ischemia Promotes Tubular Epithelial Survival

Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal ti...

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Published in:PloS one Vol. 5; no. 12; p. e14386
Main Authors: Stokman, Geurt, Stroo, Ingrid, Claessen, Nike, Teske, Gwendoline J. D., Weening, Jan J., Leemans, Jaklien C., Florquin, Sandrine
Format: Journal Article
Language:English
Published: United States Public Library of Science 21.12.2010
Public Library of Science (PLoS)
Subjects:
Animals
Antisense oligonucleotides
Apoptosis
Autocrine signalling
Basement Membrane - metabolism
c-Kit protein
Cell Biology/Cell Signaling
Cell Biology/Cellular Death and Stress Responses
Cell Survival
Epidermal growth factor
Epithelial cells
Epithelial Cells - cytology
Epithelium
Gene Expression Regulation
Hypoxia
Immunology/Immune Response
Ischemia
Ischemia - pathology
Kidney - pathology
Kidney Tubules - metabolism
Kidneys
Kinases
Ligands
Male
Mice
Mice, Inbred C57BL
Nephrology/Acute Renal Failure
Oligonucleotides
Phosphorylation
Proto-Oncogene Proteins c-kit - metabolism
Regeneration
Renal function
Reperfusion
Rodents
Stem cell factor
Stem Cell Factor - biosynthesis
Stem cells
Survival
Tubular basement membrane
Netherlands
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF) has been shown to protect the tubular epithelium against apoptosis. In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.
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Conceived and designed the experiments: GS JW JCL SF. Performed the experiments: GS IS NC GT. Analyzed the data: GS SF. Contributed reagents/materials/analysis tools: GS. Wrote the paper: GS IS JCL.
Current address: Division of Toxicology, LACDR, Leiden University, Leiden, The Netherlands
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0014386