PMID- 19443644 OWN - NLM STAT- MEDLINE DCOM- 20090901 LR - 20211020 IS - 1533-3450 (Electronic) IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 20 IP - 8 DP - 2009 Aug TI - The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of renal vasculature. PG - 1714-23 LID - 10.1681/ASN.2008060640 [doi] AB - CXC chemokine ligand 12 (CXCL12; stromal cell-derived factor 1) is a unique homeostatic chemokine that signals through its cognate receptor, CXCR4. CXCL12/CXCR4 signaling is essential for the formation of blood vessels in the gastrointestinal tract during development, but its contribution to renal development remains unclear. Here, we found that CXCL12-secreting stromal cells surround CXCR4-positive epithelial components of early nephrons and blood vessels in the embryonic kidney. In glomeruli, we observed CXCL12-secreting podocytes in close proximity to CXCR4-positive endothelial cells. Both CXCL12- and CXCR4-deficient kidneys exhibited identical phenotypes; there were no apparent abnormalities in early nephrogenesis or in differentiation of podocytes and tubules, but there was defective formation of blood vessels, including ballooning of the developing glomerular tuft and disorganized patterning of the renal vasculature. To clarify the relative importance of different cellular defects resulting from ablation of CXCL12 and CXCR4, we established endothelial cell-specific CXCR4-deficient mice, which recapitulated the renal phenotypes of conventional CXCR4-deficient mice. We conclude that CXCL12 secreted from stromal cells or podocytes acts on endothelial cells to regulate vascular development in the kidney. These findings suggest new potential therapeutic targets for remodeling the injured kidney. FAU - Takabatake, Yoshitsugu AU - Takabatake Y AD - Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine (B6), Suita, Japan. takaba@kid.med.osaka-u.ac.jp FAU - Sugiyama, Tatsuki AU - Sugiyama T FAU - Kohara, Hiroshi AU - Kohara H FAU - Matsusaka, Taiji AU - Matsusaka T FAU - Kurihara, Hidetake AU - Kurihara H FAU - Koni, Pandelakis A AU - Koni PA FAU - Nagasawa, Yasuyuki AU - Nagasawa Y FAU - Hamano, Takayuki AU - Hamano T FAU - Matsui, Isao AU - Matsui I FAU - Kawada, Noritaka AU - Kawada N FAU - Imai, Enyu AU - Imai E FAU - Nagasawa, Takashi AU - Nagasawa T FAU - Rakugi, Hiromi AU - Rakugi H FAU - Isaka, Yoshitaka AU - Isaka Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090514 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (CXCR4 protein, mouse) RN - 0 (Chemokine CXCL12) RN - 0 (Cxcl12 protein, mouse) RN - 0 (Receptors, CXCR4) SB - IM CIN - J Am Soc Nephrol. 2009 Aug;20(8):1659-61. PMID: 19608697 MH - Animals MH - Chemokine CXCL12/*metabolism MH - Endothelial Cells/metabolism MH - Kidney/blood supply/*embryology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Podocytes/metabolism MH - Receptors, CXCR4/*metabolism MH - Stromal Cells/metabolism PMC - PMC2723985 EDAT- 2009/05/16 09:00 MHDA- 2009/09/02 06:00 PMCR- 2010/08/01 CRDT- 2009/05/16 09:00 PHST- 2009/05/16 09:00 [entrez] PHST- 2009/05/16 09:00 [pubmed] PHST- 2009/09/02 06:00 [medline] PHST- 2010/08/01 00:00 [pmc-release] AID - ASN.2008060640 [pii] AID - 2008060640 [pii] AID - 10.1681/ASN.2008060640 [doi] PST - ppublish SO - J Am Soc Nephrol. 2009 Aug;20(8):1714-23. doi: 10.1681/ASN.2008060640. Epub 2009 May 14.