Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells

John R. Silkensen, Keith M Skubitz, Amy P Skubitz, David H. Chmielewski, Juan C Manivel, Jeffrey A. Dvergsten, Mark E Rosenberg

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The function of clusterin, a heterodimeric glycoprotein markedly induced in renal and other organ injuries, is unclear. Since renal injury is accompanied by alterations in cell attachment, it is possible that clusterin functions to promote cell-cell and cell-substratum interactions. In this study, a single cell suspension of renal epithelial (LLC-PK1) cells was treated with purified human clusterin, resulting in time-and dose-dependent cell aggregation. Electron microscopy of the cell aggregates demonstrated cell junction and lumen formation. To determine the effect of clusterin on cell adhesion, tissue culture plates were coated with clusterin, fibronectin, PBS, or albumin. Clusterin and fibronectin promoted cell adhesion to the same extent. The adhesion to clusterin was dose dependent and specific, as a monoclonal antibody against clusterin inhibited cell adhesion to clusterin but not fibronectin. Perturbations of the cytoskeleton may underlie the alterations in cell attachment which occur in renal injury. Induction of clusterin mRNA was seen after disruption of both microtubules and microfilaments and after inhibition of cell-substratum interactions. In conclusion, clusterin is a potent renal epithelial cell aggregation and adhesion molecule. We speculate that clusterin functions to promote cell- cell and cell-substratum interactions which are perturbed in the setting of renal injury, thereby preserving the integrity of the renal epithelial barrier.

Original languageEnglish (US)
Pages (from-to)2646-2653
Number of pages8
JournalJournal of Clinical Investigation
Volume96
Issue number6
DOIs
StatePublished - Jan 1 1995

Fingerprint

Clusterin
Swine
Epithelial Cells
Kidney
Fibronectins
Cell Adhesion
Cell Communication
Cell Aggregation
Wounds and Injuries
LLC-PK1 Cells
Intercellular Junctions
Cytoskeleton
Actin Cytoskeleton
Microtubules
Albumins

Keywords

  • acute kidney failure
  • cell communication
  • glycoprotein
  • kidney tubules
  • lipoproteins

Cite this

Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells. / Silkensen, John R.; Skubitz, Keith M; Skubitz, Amy P; Chmielewski, David H.; Manivel, Juan C; Dvergsten, Jeffrey A.; Rosenberg, Mark E.

In: Journal of Clinical Investigation, Vol. 96, No. 6, 01.01.1995, p. 2646-2653.

Research output: Contribution to journalArticle

Silkensen, John R. ; Skubitz, Keith M ; Skubitz, Amy P ; Chmielewski, David H. ; Manivel, Juan C ; Dvergsten, Jeffrey A. ; Rosenberg, Mark E. / Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells. In: Journal of Clinical Investigation. 1995 ; Vol. 96, No. 6. pp. 2646-2653.
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