title: SDF-1 activates papillary label-retaining cells during kidney repair from injury.
abstract: The adult kidney contains a population of low-cycling cells that resides in the papilla. These cells retain for long periods S-phase markers given as a short pulse early in life; i.e., they are label-retaining cells (LRC). In previous studies in adult rat and mice, we found that shortly after acute kidney injury many of the quiescent papillary LRC started proliferating (Oliver JA, Klinakis A, Cheema FH, Friedlander J, Sampogna RV, Martens TP, Liu C, Efstratiadis A, Al-Awqati Q. J Am Soc Nephrol 20: 2315-2327, 2009; Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. J Clin Invest 114: 795-804, 2004) and, with cell-tracking experiments, we found upward migration of some papillary cells including LRC (Oliver JA, Klinakis A, Cheema FH, Friedlander J, Sampogna RV, Martens TP, Liu C, Efstratiadis A, Al-Awqati Q. J Am Soc Nephrol 20: 2315-2327, 2009). To identify molecular cues involved in the activation (i.e., proliferation and/or migration) of the papillary LRC that follows injury, we isolated these cells from the H2B-GFP mice and found that they migrated and proliferated in response to the cytokine stromal cell-derived factor-1 (SDF-1). Moreover, in a papillary organ culture assay, the cell growth out of the upper papilla was dependent on the interaction of SDF-1 with its receptor Cxcr4. Interestingly, location of these two proteins in the kidney revealed a complementary location, with SDF-1 being preferentially expressed in the medulla and Cxcr4 more abundant in the papilla. Blockade of Cxcr4 in vivo prevented mobilization of papillary LRC after transient kidney ischemic injury and worsened its functional consequences. The data indicate that the SDF-1/Cxcr4 axis is a critical regulator of papillary LRC activation following transient kidney injury and during organ repair.
authors.affiliation: 1Department of Medicine, Columbia University, 630 West 168th St., New York, NY 10032, USA. jao7@columbia.edu
authors.forename: Juan A
authors.initials: JA
authors.lastname: Oliver
authors.forename: Omar
authors.initials: O
authors.lastname: Maarouf
authors.forename: Faisal H
authors.initials: FH
authors.lastname: Cheema
authors.forename: Charles
authors.initials: C
authors.lastname: Liu
authors.forename: Qing-Yin
authors.initials: QY
authors.lastname: Zhang
authors.forename: Carl
authors.initials: C
authors.lastname: Kraus
authors.forename: M
authors.initials: M
authors.lastname: Zeeshan Afzal
authors.forename: Mamoona
authors.initials: M
authors.lastname: Firdous
authors.forename: Apostolos
authors.initials: A
authors.lastname: Klinakis
authors.forename: Argiris
authors.initials: A
authors.lastname: Efstratiadis
authors.forename: Qais
authors.initials: Q
authors.lastname: Al-Awqati
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007674:Kidney Diseases / Q000473:pathology* / Q000503:physiopathology; D007679:Kidney Medulla / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D007202:Indicators and Reagents; D019718:Receptors, CXCR4