Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury.
BACKGROUND
Stem cell and leukocyte migration during homeostasis and inflammation is regulated by a number of chemokines. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are important mediators of leukocyte homeostasis. The postischemic kidney has been shown to recruit different leukocyte populations, including bone marrow-derived stem cells. Therefore, we investigated the SDF-1/CXCR4 system in the kidney after ischemic acute renal failure (ARF).


METHODS
We used immunohistochemistry, in situ hybridization, enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR) to detect SDF-1 and CXCR4 in the normal kidney and the kidney after ischemia/reperfusion (I/R) ARF. Mobilization was assessed by flow cytometry for CD34 and colony assays.


RESULTS
We show that SDF-1 is expressed in the normal mouse kidney and tubular cells express CXCR4. SDF-1 expression in the kidney increases after I/R induced ARF and decreases in the bone marrow, thereby reversing the normal gradient between bone marrow and the periphery. This causes mobilization of CD34-positive cells into the circulation and their subsequent homing to the kidney with ARF. In vitro and in vivo chemotaxis of bone marrow cells toward damaged kidney epithelium is reversibly inhibited by anti-CXCR4 antibodies.


CONCLUSIONS
Our data show that renal SDF-1 is a currently unrecognized mediator of homing to and migration of CXCR4 expressing cells in the injured kidney. Because certain cells that express CXCR4 may have renoprotective effects, our results suggest that SDF-1 may be a major signal involved in kidney repair.
Tögel
Florian
F
Department of Medicine, Division of Nephrology, University of Utah and VA Medical Centers, Salt Lake City, Utah 84148, USA.
Isaac
Jorge
J
Hu
Zhuma
Z
Weiss
Kathy
K
Westenfelder
Christof
C
D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017403:In Situ Hybridization; D007668:Kidney / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D015854:Up-Regulation
D018952:Antigens, CD34; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012333:RNA, Messenger; D019718:Receptors, CXCR4