The role of ADAM 15 in glomerular mesangial cell migration

Martin, John, Eynstone, Lisa V., Davies, Malcolm, Williams, John David and Steadman, Robert ORCID: https://orcid.org/0000-0002-1303-2496 2002. The role of ADAM 15 in glomerular mesangial cell migration. The Journal of Biological Chemistry 277 (37) , pp. 33683-33689. 10.1074/jbc.M200988200

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Abstract

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 migration in 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	1083-351X
Last Modified:	17 Oct 2022 08:33
URI:	https://orca.cardiff.ac.uk/id/eprint/460

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