The role of cell-extracellular matrix interactions in glomerular injury

Exp Cell Res. 2012 May 15;318(9):1001-10. doi: 10.1016/j.yexcr.2012.02.033. Epub 2012 Mar 5.

Abstract

Glomerulosclerosis is characterized by excessive deposition of extracellular matrix within the glomeruli of the kidney, glomerular cell death, and subsequent loss of functional glomeruli. While in physiological situations the levels of extracellular matrix components are kept constant by a tight balance between formation and degradation, in the case of injury that results in fibrosis there is increased matrix deposition relative to its breakdown. Multiple factors control matrix synthesis and degradation, thus contributing to the development of glomerulosclerosis. This review focuses primarily on the role of cell-matrix interactions, which play a critical role in governing glomerular cell cues in both healthy and diseased kidneys. Cell-extracellular matrix interactions are made possible by various cellular receptors including integrins, discoidin domain receptors, and dystroglycan. Upon binding to a selective extracellular matrix protein, these receptors activate intracellular signaling pathways that can either downregulate or upregulate matrix synthesis and deposition. This, together with the observation that changes in the expression levels of matrix receptors have been documented in glomerular disease, clearly emphasizes the contribution of cell-matrix interactions in glomerular injury. Understanding the molecular mechanisms whereby extracellular matrix receptors regulate matrix homeostasis in the course of glomerular injury is therefore critical for devising more effective therapies to treat and ideally prevent glomerulosclerosis.

Publication types

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

MeSH terms

  • Animals
  • Extracellular Matrix / metabolism*
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Humans
  • Integrins / metabolism
  • Kidney / metabolism
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology

Substances

  • Integrins