SDF-1 provides morphological and functional protection against renal ischaemia/reperfusion injury.
BACKGROUND
The chemokine stromal cell-derived factor-1 (SDF-1) is thought to be involved in mediating tissue repair by promoting migration of bone marrow stem or progenitor cells to the site of injury. Increased levels of renal SDF-1 are found after kidney injury. However, recently, we showed that SDF-1 does not play an important role in the migration of haematopoietic stem cells to the post-ischaemic kidney. The function of increased post-ischaemic renal SDF-1 expression in modulating renal ischaemia/reperfusion injury remains, therefore, unknown.


METHODS
We studied the role of SDF-1 in renal ischaemia/reperfusion injury by locally decreasing SDF-1 expression and subsequent SDF-1 signalling in the corticomedullary region of the kidney using antisense oligonucleotide treatment in mice.


RESULTS
Renal SDF-1 protein increased significantly in the early phase of ischaemia/reperfusion injury. Antisense treatment resulted in a reduction of corticomedullary SDF-1 expression which was accompanied by severely increased tubular injury and decreased renal function. We did not observe any difference in mobilization or retention of CXCR4-positive haematopoietic stem or progenitor cells after induction of renal ischaemia. Rather, antisense-treated animals showed markedly increased apoptosis of the tubular epithelium accompanied by an increased renal inflammatory response. Conclusions. These data indicate a new role for SDF-1 in renal pathogenesis by mediating tubular epithelial protection against ischaemic injury and suggest that SDF-1 by itself is not crucial for the influx of haematopoietic stem or progenitor cells towards the ischaemic injured kidney.
Stokman
Geurt
G
Department of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Stroo
Ingrid
I
Claessen
Nike
N
Teske
Gwendoline J D
GJ
Florquin
Sandrine
S
Leemans
Jaklien C
JC
D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D016376:Oligonucleotides, Antisense