Update of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis

Yashpal S. Kanwar, Jun Wada, Sun Lin, Farhad R. Danesh, Sumant S. Chugh, Qiwei Yang, Tushar Banerjee, Jon W. Lomasney

Research output: Contribution to journalReview article

53 Scopus citations

Abstract

One of the hallmarks of mammalian nephrogenesis includes a mesenchymal-epithelial transition that is accomplished by intercalation of the ureteric bud, an epithelium-lined tubelike structure, into an undifferentiated mesenchyme, and the latter then undergoes an inductive transformation and differentiates into an epithelial phenotype. At the same time, the differentiating mesenchyme reciprocates by inducing branching morphogenesis of the ureteric bud, which forms a treelike structure with dichotomous iterations. These reciprocal inductive interactions lead to the development of a functioning nephron unit made up of a glomerulus and proximal and distal tubules. The inductive interactions and differentiation events are modulated by a number of transcription factors, protooncogenes, and growth factors and their receptors, which regulate the expression of target morphogenetic modulators including the ECM, integrin receptors, and cell adhesion molecules. These target macromolecules exhibit spatiotemporal and stage-specific developmental regulation in the metanephros. The ECM molecules expressed at the epithelial-mesenchymal interface are perhaps the most relevant and conducive to the paracrine-juxtacrine interactions in a scenario where the ligand is expressed in the mesenchyme while the receptor is located in the ureteric bud epithelium or vice versa. In addition, expression of the target ECM macromolecules is regulated by matrix metalloproteinases and their inhibitors to generate a concentration gradient at the interface to further propel epithelial-mesenchymal interactions so that nephrogenesis can proceed seamlessly. In this review, we discuss and update our current understanding of the role of the ECM and related macromolecules with respect to metanephric development.

Original languageEnglish (US)
Pages (from-to)F202-F215
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number2 55-2
Publication statusPublished - Feb 1 2004

    Fingerprint

Keywords

  • Integrins
  • Metalloproteinases
  • Renal development

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Kanwar, Y. S., Wada, J., Lin, S., Danesh, F. R., Chugh, S. S., Yang, Q., ... Lomasney, J. W. (2004). Update of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis. American Journal of Physiology - Renal Physiology, 286(2 55-2), F202-F215.