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

Nephrol Dial Transplant. 2002:17 Suppl 9:75-7. doi: 10.1093/ndt/17.suppl_9.75.

Abstract

Mammalian nephrogenesis is modulated by a number of extracellular matrix (ECM) glycoproteins, integrins and cell adhesion molecules. We demonstrated the existence of integrins alphavbeta1, alphavbeta3, alphavbeta5 and alphavbeta6 in epithelial elements of developing nephrons. Fibrillin-1 is a putative ligand for integrin alphavbeta3, and tubulointerstitial nephritis antigen (TIN-ag) is a ligand for integrins alphavbeta3 and alpha3beta1. 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 alphav-related integrins and their ligands play an important role in mammalian nephrogenesis. Recently identified modulators of cell-matrix interactions, i.e. beta-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Embryonic and Fetal Development / physiology
  • Extracellular Matrix / metabolism*
  • Humans
  • Integrin beta Chains / metabolism*
  • Kidney / enzymology*
  • Organ Culture Techniques
  • Receptors, Cell Surface / metabolism*

Substances

  • Integrin beta Chains
  • Receptors, Cell Surface
  • extracellular matrix receptor