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.
Department of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Geurt
G
Stokman
Ingrid
I
Stroo
Nike
N
Claessen
Gwendoline J D
GJ
Teske
Sandrine
S
Florquin
Jaklien C
JC
Leemans
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