Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity

Sarah Netzel-Arnett; David J Mitola; Susan S Yamada; Kali Chrysovergis; Kenn Holmbeck; Henning Birkedal-Hansen; Thomas H Bugge

doi:10.1074/jbc.M206354200

Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity

Sarah Netzel-Arnett, David J Mitola, Susan S Yamada, Kali Chrysovergis, Kenn Holmbeck, Henning Birkedal-Hansen, Thomas H Bugge

66 Citationer (Scopus)

Abstract

Matrix metalloproteinase-14 is required for degradation of fibrillar collagen by mesenchymal cells. Here we show that keratinocytes use an alternative plasminogen and matrix metalloproteinase-13-dependent pathway for dissolution of collagen fibrils. Primary keratinocytes displayed an absolute requirement for serum to dissolve collagen. Dissolution of collagen was abolished in plasminogen-depleted serum and could be restored by the exogenous addition of plasminogen. Both plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase blocked collagen dissolution, demonstrating the requirement of both plasminogen activation and matrix metalloproteinase activity for degradation. Cell surface plasmin activity was critical for the degradation process as aprotinin, but not alpha(2)-antiplasmin, prevented collagen dissolution. Keratinocytes with single deficiencies in either urokinase or tissue plasminogen activator retained the ability to dissolve collagen. However, collagen fibril dissolution was abolished in keratinocytes with a combined deficiency in both urokinase and tissue plasminogen activator. Combined, but not single, urokinase and tissue plasminogen activator deficiency also completely blocked the activation of the fibrillar collagenase, matrix metalloproteinase-13, by keratinocytes. The activation of matrix metalloproteinase-13 in normal keratinocytes was prevented by plasminogen activator inhibitor-1 and aprotinin but not by tissue inhibitor of metalloproteinase-1 and -2, suggesting that plasmin activates matrix metalloproteinase-13 directly. We propose that plasminogen activation facilitates keratinocyte-mediated collagen breakdown via the direct activation of matrix metalloproteinase-13 and possibly other fibrillar collagenases.

Originalsprog	Engelsk
Tidsskrift	The Journal of Biological Chemistry
Vol/bind	277
Udgave nummer	47
Sider (fra-til)	45154-61
Antal sider	8
ISSN	0021-9258
DOI	https://doi.org/10.1074/jbc.M206354200
Status	Udgivet - 22 nov. 2002

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10.1074/jbc.M206354200

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title = "Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity",

abstract = "Matrix metalloproteinase-14 is required for degradation of fibrillar collagen by mesenchymal cells. Here we show that keratinocytes use an alternative plasminogen and matrix metalloproteinase-13-dependent pathway for dissolution of collagen fibrils. Primary keratinocytes displayed an absolute requirement for serum to dissolve collagen. Dissolution of collagen was abolished in plasminogen-depleted serum and could be restored by the exogenous addition of plasminogen. Both plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase blocked collagen dissolution, demonstrating the requirement of both plasminogen activation and matrix metalloproteinase activity for degradation. Cell surface plasmin activity was critical for the degradation process as aprotinin, but not alpha(2)-antiplasmin, prevented collagen dissolution. Keratinocytes with single deficiencies in either urokinase or tissue plasminogen activator retained the ability to dissolve collagen. However, collagen fibril dissolution was abolished in keratinocytes with a combined deficiency in both urokinase and tissue plasminogen activator. Combined, but not single, urokinase and tissue plasminogen activator deficiency also completely blocked the activation of the fibrillar collagenase, matrix metalloproteinase-13, by keratinocytes. The activation of matrix metalloproteinase-13 in normal keratinocytes was prevented by plasminogen activator inhibitor-1 and aprotinin but not by tissue inhibitor of metalloproteinase-1 and -2, suggesting that plasmin activates matrix metalloproteinase-13 directly. We propose that plasminogen activation facilitates keratinocyte-mediated collagen breakdown via the direct activation of matrix metalloproteinase-13 and possibly other fibrillar collagenases.",

keywords = "Animals, Animals, Newborn, Cells, Cultured, Collagen/metabolism, Collagenases/metabolism, Culture Media, Serum-Free, Enzyme Activation, Female, Fibroblasts/cytology, Gene Targeting, Humans, Keratinocytes/cytology, Male, Matrix Metalloproteinase 13, Matrix Metalloproteinases, Membrane-Associated, Metalloendopeptidases/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Plasminogen/metabolism, Plasminogen Activator Inhibitor 1/metabolism, Plasminogen Activators/genetics, Receptors, Cell Surface/genetics, Receptors, Urokinase Plasminogen Activator, Serine Proteinase Inhibitors/metabolism, Tissue Inhibitor of Metalloproteinases/metabolism, Tissue Plasminogen Activator/genetics, Urokinase-Type Plasminogen Activator/genetics",

author = "Sarah Netzel-Arnett and Mitola, {David J} and Yamada, {Susan S} and Kali Chrysovergis and Kenn Holmbeck and Henning Birkedal-Hansen and Bugge, {Thomas H}",

year = "2002",

month = nov,

day = "22",

doi = "10.1074/jbc.M206354200",

language = "English",

volume = "277",

pages = "45154--61",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

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T1 - Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity

AU - Netzel-Arnett, Sarah

AU - Mitola, David J

AU - Yamada, Susan S

AU - Chrysovergis, Kali

AU - Holmbeck, Kenn

AU - Birkedal-Hansen, Henning

AU - Bugge, Thomas H

PY - 2002/11/22

Y1 - 2002/11/22

N2 - Matrix metalloproteinase-14 is required for degradation of fibrillar collagen by mesenchymal cells. Here we show that keratinocytes use an alternative plasminogen and matrix metalloproteinase-13-dependent pathway for dissolution of collagen fibrils. Primary keratinocytes displayed an absolute requirement for serum to dissolve collagen. Dissolution of collagen was abolished in plasminogen-depleted serum and could be restored by the exogenous addition of plasminogen. Both plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase blocked collagen dissolution, demonstrating the requirement of both plasminogen activation and matrix metalloproteinase activity for degradation. Cell surface plasmin activity was critical for the degradation process as aprotinin, but not alpha(2)-antiplasmin, prevented collagen dissolution. Keratinocytes with single deficiencies in either urokinase or tissue plasminogen activator retained the ability to dissolve collagen. However, collagen fibril dissolution was abolished in keratinocytes with a combined deficiency in both urokinase and tissue plasminogen activator. Combined, but not single, urokinase and tissue plasminogen activator deficiency also completely blocked the activation of the fibrillar collagenase, matrix metalloproteinase-13, by keratinocytes. The activation of matrix metalloproteinase-13 in normal keratinocytes was prevented by plasminogen activator inhibitor-1 and aprotinin but not by tissue inhibitor of metalloproteinase-1 and -2, suggesting that plasmin activates matrix metalloproteinase-13 directly. We propose that plasminogen activation facilitates keratinocyte-mediated collagen breakdown via the direct activation of matrix metalloproteinase-13 and possibly other fibrillar collagenases.

AB - Matrix metalloproteinase-14 is required for degradation of fibrillar collagen by mesenchymal cells. Here we show that keratinocytes use an alternative plasminogen and matrix metalloproteinase-13-dependent pathway for dissolution of collagen fibrils. Primary keratinocytes displayed an absolute requirement for serum to dissolve collagen. Dissolution of collagen was abolished in plasminogen-depleted serum and could be restored by the exogenous addition of plasminogen. Both plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase blocked collagen dissolution, demonstrating the requirement of both plasminogen activation and matrix metalloproteinase activity for degradation. Cell surface plasmin activity was critical for the degradation process as aprotinin, but not alpha(2)-antiplasmin, prevented collagen dissolution. Keratinocytes with single deficiencies in either urokinase or tissue plasminogen activator retained the ability to dissolve collagen. However, collagen fibril dissolution was abolished in keratinocytes with a combined deficiency in both urokinase and tissue plasminogen activator. Combined, but not single, urokinase and tissue plasminogen activator deficiency also completely blocked the activation of the fibrillar collagenase, matrix metalloproteinase-13, by keratinocytes. The activation of matrix metalloproteinase-13 in normal keratinocytes was prevented by plasminogen activator inhibitor-1 and aprotinin but not by tissue inhibitor of metalloproteinase-1 and -2, suggesting that plasmin activates matrix metalloproteinase-13 directly. We propose that plasminogen activation facilitates keratinocyte-mediated collagen breakdown via the direct activation of matrix metalloproteinase-13 and possibly other fibrillar collagenases.

KW - Animals

KW - Animals, Newborn

KW - Cells, Cultured

KW - Collagen/metabolism

KW - Collagenases/metabolism

KW - Culture Media, Serum-Free

KW - Enzyme Activation

KW - Female

KW - Fibroblasts/cytology

KW - Gene Targeting

KW - Humans

KW - Keratinocytes/cytology

KW - Male

KW - Matrix Metalloproteinase 13

KW - Matrix Metalloproteinases, Membrane-Associated

KW - Metalloendopeptidases/metabolism

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Plasminogen/metabolism

KW - Plasminogen Activator Inhibitor 1/metabolism

KW - Plasminogen Activators/genetics

KW - Receptors, Cell Surface/genetics

KW - Receptors, Urokinase Plasminogen Activator

KW - Serine Proteinase Inhibitors/metabolism

KW - Tissue Inhibitor of Metalloproteinases/metabolism

KW - Tissue Plasminogen Activator/genetics

KW - Urokinase-Type Plasminogen Activator/genetics

U2 - 10.1074/jbc.M206354200

DO - 10.1074/jbc.M206354200

M3 - Journal article

C2 - 12192005

SN - 0021-9258

VL - 277

SP - 45154

EP - 45161

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 47

ER -

Collagen dissolution by keratinocytes requires cell surface plasminogen activation and matrix metalloproteinase activity

Abstract

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