ADHESION OF HUMAN GLOMERULAR CELL TO MATRIX

  • Cosio, Fernando G (PI)

Project: Research project

Project Details

Description

The purpose of the present studies is to evaluate the effects of
immune complexes (IC) formation and complement activation on the
attachment of human glomerular cells to the extracellular matrix.
Cell-matrix and cell-cell adhesion are mediated by a series of cell
membrane proteins called integrins. By mediating cell-matrix adhesion,
integrins influence cell morphology, cell proliferation and a variety of
cell functions. In addition, certain integrins also function as
receptors that is, binding to those integrins modify cell function. We
recently demonstrated that several integrins are present in human
glomerular cells and one of those integrins, a fibronectin (FN) receptor,
mediate the binding of human mesangial cells (MC) to FN and the
phagocytosis of FN coated particles. It is difficult to assess directly
the relevance of cell-matrix adhesion to whole kidney function. However,
previous studies have suggested that the attachment of glomerular
epithelial cells to the glomerular basement membrane determines, at least
in part, the selectivity permeability of the glomerular filter. Because IC and complement are common mediators of glomerular
injury in humans, in preliminary studies we assessed whether those
pathogenic events may produce alterations on the adhesion of MC to
matrix. We showed that complement activation by IC result in detachment
of MC from matrix, an event not associated with cell death. We also
showed that MC-matrix detachment is an active process that requires new
RNA and protein synthesis. In the present application, we propose to
evaluate the mechanisms responsible for glomerular cell-matrix detachment
after exposure to complement. Preliminary studies presented here and
previous studies from our laboratory showed that complement activation
increases glomerular cell synthesis of a variety of proteins. This
effect of complement may have pathogenic relevance by increasing
synthesis of proteins normally produced by glomerular cells, such as
integrins and matrix proteins, and/or by inducing synthesis of new
proteins, such as heat shock proteins. The effects of complement on the
synthesis of these particular groups of proteins by glomerular cells will
be evaluated here. These observations provide new insights into
mechanisms by which complement activation can modify cell function and
produce cell damage. Because cell-matrix adhesion plays a role in
maintaining normal kidney structure and function, the present studies are
likely to also give new insights into pathogenic mechanisms involved in
complement-mediated glomerulonephritis.
StatusFinished
Effective start/end date6/1/915/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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