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Nephrol Dial Transplant (2002) 17: 75-77
© 2002 European Renal Association-European Dialysis and Transplant Association


Model of Kidney Development

Relevance of extracellular matrix and its receptors in mammalian nephrogenesis revealed by metanephric organ culture system

Jun Wada, Yashpal S. Kanwar1 and Hirofumi Makino

Okayama University Graduate School of Medicine and Densitry, Okayama, Japan and 1 Northwestern University Medical School, Chicago, USA

Abstract

Mammalian nephrogenesis is modulated by a number of extracellular matrix (ECM) glycoproteins, integrins and cell adhesion molecules. We demonstrated the existence of integrins {alpha}vß1, {alpha}vß3, {alpha}vß5 and {alpha}vß6 in epithelial elements of developing nephrons. Fibrillin-1 is a putative ligand for integrin {alpha}vß3, and tubulointerstitial nephritis antigen (TIN-ag) is a ligand for integrins {alpha}vß3 and {alpha}3ß1. Fibrillin-1 and TIN-ag are also differentially expressed in the developing kidney. The inclusion of antisense oligonucleotide in a mouse kidney organ culture system indicated that the {alpha}v-related integrins and their ligands play an important role in mammalian nephrogenesis. Recently identified modulators of cell–matrix interactions, i.e. ß-galactoside-binding mammalian lectins (galectins), are involved in cell–cell and cell–matrix interactions by cross-linking glycoconjugates located on the ECM and membrane-bound glycoproteins. We identified and cloned a new member of the galectins from embryonic kidneys, and designated it galectin-9. Since high glucose alters the expression of ECM proteins and integrins, we also investigated the influence of glucose on metanephric development. The presence of 30 mM D-glucose in metanephric organ culture induced dysmorphogenesis of the kidney accompanied by decreased expression of perlecan. Furthermore, we screened the genes differentially expressed under high glucose conditions in streptozotocin-induced newborn mouse kidneys by representational difference analysis of cDNA. We identified translocase of inner mitochondrial membrane (Tim44) and renal-specific oxido-reductase (RSOR). The roles of these molecules in glucose-induced dysmorphogenesis and the relationship with ECM-related molecules need to be addressed.

Keywords: fibrillin-1; galectin-9; integrin {alpha}v; Tim44; TIN-ag

Notes

Correspondence and offprint requests to: Jun Wada, MD, PhD, Department of Medicine and Clinical Science (Department of Medicine III), Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.


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