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

Jun Wada, Yashpal S. Kanwar, Hirofumi Makino

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6 Citations (Scopus)

Abstract

Mammalian nephrogenesis is modulated by a number of extracellular matrix (ECM) glycoproteins, integrins and cell adhesion molecules. We demonstrated the existence of integrins αvβ1, αvβ3, αvβ5 and αvβ6 in epithelial elements of developing nephrons. Fibrillin-1 is a putative ligand for integrin αvβ3, and tubulo-interstitial nephritis antigen (TIN-ag) is a ligand for integrins αvβ3 and α31. 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 αv-related integrins and their ligands play an important role in mammalian nephrogenesis. Recently identified modulators of cell-matrix interactions, i.e. β-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.

Original languageEnglish
Pages (from-to)75-77
Number of pages3
JournalNephrology Dialysis Transplantation
Volume17
Issue numberSUPPL. 9
Publication statusPublished - 2002

Fingerprint

Organ Culture Techniques
Integrins
Kidney
Galactosides
Glucose
Lectins
Extracellular Matrix
Interstitial Nephritis
Ligands
Cell Communication
Antigens
Glycoconjugates
Antisense Oligonucleotides
Extracellular Matrix Proteins
Nephrons
Membrane Glycoproteins
Cell Adhesion Molecules
Mitochondrial Membranes
Streptozocin
extracellular matrix receptor

Keywords

  • Fibrilin-1
  • Galectin-9
  • Integrin αv
  • Tim44
  • TIN-ag

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

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abstract = "Mammalian nephrogenesis is modulated by a number of extracellular matrix (ECM) glycoproteins, integrins and cell adhesion molecules. We demonstrated the existence of integrins αvβ1, αvβ3, αvβ5 and αvβ6 in epithelial elements of developing nephrons. Fibrillin-1 is a putative ligand for integrin αvβ3, and tubulo-interstitial nephritis antigen (TIN-ag) is a ligand for integrins αvβ3 and α31. 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 αv-related integrins and their ligands play an important role in mammalian nephrogenesis. Recently identified modulators of cell-matrix interactions, i.e. β-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.",
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