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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Vydané v:	PloS one Ročník 5; číslo 12; s. e14386
Hlavní autori:	Stokman, Geurt, Stroo, Ingrid, Claessen, Nike, Teske, Gwendoline J. D., Weening, Jan J., Leemans, Jaklien C., Florquin, Sandrine
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 21.12.2010 Public Library of Science (PLoS)
Predmet:	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
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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