Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells.

Abstract

The function of clusterin, a heterodimeric glycoprotein markedly induced in renal and other organ injuries, is un-clear. 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 timeand 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. (J. Clin. Invest. 1995Invest. . 96:2646Invest. -2653

Silencing Expression of the Clusterin/Apolipoprotein J Gene in Human Cancer Cells Using Small Interfering RNA Induces Spontaneous Apoptosis, Reduced Growth Ability, and Cell Sensitization to Genotoxic and Oxidative Stress

“…By analyzing the expression levels of other recently identified CLU protein forms, to our surprise, we found that the Cl-I and Cl-II oligonucleotides did not exert any significant effect on the putative 55 kDa (n-CLU 55 ) CLU protein form in both KH OS and U-2 OS cells; only a minor effect on the 49 kDa c-CLU 49 protein form level was detected (Fig. 6, A and B), although the binding sites of the Cl-I or the Cl-II oligonucleotides are common between the s-CLU and n-CLU mRNAs (5).…”

“…Maturation of the primary translation molecule include disulfide bonding, conversion to a high-mannose endoplasmic reticulum-associated form of ϳ60 kDa, extensive additional N-linked glycozylation, and finally, proteolytic cleavage in the trans-Golgi compartments that result in the mature secreted heterodimeric CLU protein form of ϳ70 -80 kDa (3). Interestingly, another CLU protein form of ϳ55 kDa, designated as nuclear (n)-CLU 55 (4), has been recently described in MCF-7 cells. According to a recent study (5), this protein form originates, after apoptosis induction, from a 49-kDa primary product (c-CLU 49 ) that is translated from an alternatively spliced CLU transcript.…”

From Humans to Experimental Models: The Cytoprotective Role of Clusterin in the Kidney

“…The biological activities of extracellular sCLU have been studied extensively; it was initially found to induce cell aggregation [39][40][41], and in the plasma it inhibited the cytolysis of complement membrane attack complex (MAC) by binding to the complement components [42][43][44], and was associated with both high-density lipoprotein (HDL) and low-density lipoprotein (LDL) complexes [33,45,46]. These studies suggest that sCLU in the blood may serve not only as an inhibitor of the lytic terminal complement cascade, but also as a regulator of lipid transport and local lipid redistribution.…”

Presence, localization, and origin of clusterin in normal human spermatozoa

“…The human homolog of clusterin has also been given other names, including complement-lysis inhibitor (CLI), secreted protein 40 (SP-40), and apolipoprotein J (ApoJ). Clusterin participates in many biological processes such as cell adhesion, lipid transportation, complement inhibition, membrane recycling and apoptosis [15,30,31,34,36,41]. High levels of clusterin expression have been found to be positively correlated with severe pathophysiological states and conditions such as renal disease, neurodegenerative disease, atherosclerosis, myocardial infarction and cancer [6,10,27,37,40].…”