Rat glomerular mesangial cells require laminin-9 to migrate in response to insulin-like growth factor binding protein-5

1 Department of Medicine, School of Medicine, University of Washington; and 2 Veterans Affairs Puget Sound Health Care System, Seattle, Washington Submitted 13 December 2005 ; accepted in final form 25 April 2006 Temporal and spatial differences in extracellular matrix play critical roles in cell pr...

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Published in:American Journal of Physiology: Cell Physiology 2006-10, Vol.291 (4), p.C589-C599
Main Authors: Berfield, Anne K, Hansen, Kim M, Abrass, Christine K
Format: Article
Language:English
Subjects:
Animals
Cell Membrane - metabolism
Cell Movement - drug effects
Cell Movement - physiology
Cells, Cultured
Cellular biology
Gene expression
Insulin
Insulin-Like Growth Factor Binding Protein 5 - pharmacology
Integrin alpha6beta1 - antagonists & inhibitors
Laminin - antagonists & inhibitors
Laminin - genetics
Laminin - metabolism
Laminin - physiology
Mesangial Cells - drug effects
Mesangial Cells - metabolism
Mesangial Cells - physiology
Migration
Oligonucleotides, Antisense - pharmacology
Proteins
Rats
RNA, Messenger - metabolism
Studies
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Summary:1 Department of Medicine, School of Medicine, University of Washington; and 2 Veterans Affairs Puget Sound Health Care System, Seattle, Washington Submitted 13 December 2005 ; accepted in final form 25 April 2006 Temporal and spatial differences in extracellular matrix play critical roles in cell proliferation, differentiation and migration. Different migratory stimuli use different substrates and receptors to achieve cell migration. To understand the mechanism of insulin-like growth factor binding protein-5 (IGFBP-5)-induced migration in mesangial cells, the roles of integrins and substrates were examined. IGFBP-5 induced an increase in mRNA expression for laminin (LN) chains lama4 , lamb2 , and lamc1 , suggesting that LN-9 might be required for migration. Antibodies to the LN 4 and LN 2 chains, but not LN 1 , blocked IGFBP-5-induced migration. Anti-sense morpholino oligonucleotide inhibition of expression of LN 4 substantially reduced expression of LN-8/9 ( 4 1 1 / 4 2 1 , 411/421) and prevented IGFBP-5-induced migration. Anti-sense inhibition of lamb2 reduced expression of LN-9. Absence of LN-9 prevented IGFBP-5-induced migration, which was not preserved by continued expression of LN-8. The requirement for LN-9 was further supported by studies of T98G cells, which express predominantly LN-8. IGFBP-5 had little effect on migration in these cells, but increased migration when T98G cells were plated on LN-8/9. IGFBP-5-mediated mesangial cell migration was inhibited by antibodies that block attachment to 6 1 -integrins but was unaffected by antibodies and disintegrins that block binding to other integrins. Furthermore, in cells with anti-sense inhibited expression of LN-9, integrin 6 1 was no longer detected on the cell surface. These studies suggest the specificity of mechanisms of migration induced by specific stimuli and for the first time demonstrate a unique function for LN-9 in mediating IGFBP-5-induced migration. migration; integrins; extracellular matrix Address for reprint requests and other correspondence: C. K. Abrass, Univ. of Washington, Dept. of Medicine, South Lake Union, 815 Mercer St., Seattle, WA 98109 (e-mail: cabrass{at}u.washington.edu )
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00623.2005