The Role of ADAM 15 in Glomerular Mesangial Cell Migration

Mesangial cells (MC) occupy the core of the renal glomerulus and are surrounded by a mesangial matrix. In certain diseases, MC migrate through this matrix into the pericapillary space. The mechanisms involved, however, are poorly understood. Members of the ADAM (A Disintegrin And Metalloproteinase)...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-09, Vol.277 (37), p.33683-33689
Main Authors: Martin, John, Eynstone, Lisa V., Davies, Malcolm, Williams, John D., Steadman, Robert
Format: Article
Language:English
Subjects:
ADAM Proteins
Blotting, Western
Cell Movement
Cells, Cultured
Gelatin - metabolism
Glomerular Mesangium - cytology
Humans
Membrane Proteins - antagonists & inhibitors
Membrane Proteins - physiology
Metalloendopeptidases - antagonists & inhibitors
Metalloendopeptidases - physiology
Reverse Transcriptase Polymerase Chain Reaction
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Summary:Mesangial cells (MC) occupy the core of the renal glomerulus and are surrounded by a mesangial matrix. In certain diseases, MC migrate through this matrix into the pericapillary space. The mechanisms involved, however, are poorly understood. Members of the ADAM (A Disintegrin And Metalloproteinase) family of membrane proteins have the potential to be key modulators of cell-matrix interactions through the activities of their constituent domains. We have studied the possible role of ADAM 15 in human (H) MC migrationin vitro. HMC ADAM 15 was expressed at low levels in serum-free medium but was increased during migration. Antibodies to the individual domains of ADAM 15 and the incorporation of antisense ADAM 15, (but not control oligonucleotide) inhibited this migration. Furthermore, inhibition of migration by the broad spectrum metalloproteinase inhibitor BB3103, demonstrated that metalloproteinase activity was essential for migration. ADAM 15, extracted from HMC membranes, was an active metalloproteinase, which degraded both type IV collagen and gelatin prepared from fibrillar collagen. Activity was inhibited by EDTA but not by phenylmethylsulfonyl fluoride. This is the first report of the potential of ADAM 15 for involvement in the restructuring of the mesangial matrix and in the migration of MC in disease.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M200988200