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Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts

Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts
Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts
BackgroundIn bronchial asthma, subepithelial fibrosis in the conducting airways is associated with increased numbers of subepithelial fibroblasts.
ObjectiveThis study examined the hypothesis that MMP-2 from airway epithelial cells induces the proliferation of subepithelial fibroblasts.
MethodsUsing primary bronchial epithelial cells MMP-2, MT1-MMP and TIMP-2 mRNA expression were assessed by Northern blotting and RT-PCR. Primary bronchial epithelial cells transfected with constructs encoding pro-MMP-2 and MT1-MMP (MMP-14).
ResultsTransfected cells showed enhanced expression of the appropriate mRNA species by RT-PCR and enhanced MMP-2 or MT1-MMP activity by zymography. Active MMP-2 levels in epithelial supernatants were increased most by cotransfection with pro-MMP-2 and MT1-MMP encoding constructs. By measuring tritiated thymidine incorporation, supernatants from transfected cells were found to enhance DNA synthesis of primary airway fibroblast cultures compared with controls. There was a strong correlation (r = 0.9, P < 0.01) between MMP-2 levels in epithelial cell conditioned media and fibroblast proliferation as indicated by DNA synthesis. The MMP inhibitor 1,10-phenanthroline attenuated the increased proliferation, while the addition of exogenous purified MMP-2 alone also increased fibroblast proliferation.
ConclusionsOur results support a role for MMP-2 in mediating cross-talk between epithelial cells and myofibroblasts.
0954-7894
881-888
Xu, J.
caa6a307-ce55-4e76-9da4-0d8be2895651
Benyon, R.C.
11d7f1b7-3974-497e-9169-acd695de45ee
Leir, S.H.
8b286b20-8054-4fff-a8e5-c5e3a13bcbba
Zhang, S.
76640b2c-83c0-4a90-bcd8-939ffb2505aa
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Lackie, P.M.
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Xu, J.
caa6a307-ce55-4e76-9da4-0d8be2895651
Benyon, R.C.
11d7f1b7-3974-497e-9169-acd695de45ee
Leir, S.H.
8b286b20-8054-4fff-a8e5-c5e3a13bcbba
Zhang, S.
76640b2c-83c0-4a90-bcd8-939ffb2505aa
Holgate, S.T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Lackie, P.M.
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a

Xu, J., Benyon, R.C., Leir, S.H., Zhang, S., Holgate, S.T. and Lackie, P.M. (2002) Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts. Clinical & Experimental Allergy, 32 (6), 881-888. (doi:10.1046/j.1365-2745.2002.01386.x).

Record type: Article

Abstract

BackgroundIn bronchial asthma, subepithelial fibrosis in the conducting airways is associated with increased numbers of subepithelial fibroblasts.
ObjectiveThis study examined the hypothesis that MMP-2 from airway epithelial cells induces the proliferation of subepithelial fibroblasts.
MethodsUsing primary bronchial epithelial cells MMP-2, MT1-MMP and TIMP-2 mRNA expression were assessed by Northern blotting and RT-PCR. Primary bronchial epithelial cells transfected with constructs encoding pro-MMP-2 and MT1-MMP (MMP-14).
ResultsTransfected cells showed enhanced expression of the appropriate mRNA species by RT-PCR and enhanced MMP-2 or MT1-MMP activity by zymography. Active MMP-2 levels in epithelial supernatants were increased most by cotransfection with pro-MMP-2 and MT1-MMP encoding constructs. By measuring tritiated thymidine incorporation, supernatants from transfected cells were found to enhance DNA synthesis of primary airway fibroblast cultures compared with controls. There was a strong correlation (r = 0.9, P < 0.01) between MMP-2 levels in epithelial cell conditioned media and fibroblast proliferation as indicated by DNA synthesis. The MMP inhibitor 1,10-phenanthroline attenuated the increased proliferation, while the addition of exogenous purified MMP-2 alone also increased fibroblast proliferation.
ConclusionsOur results support a role for MMP-2 in mediating cross-talk between epithelial cells and myofibroblasts.

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Published date: 2002

Identifiers

Local EPrints ID: 27498
URI: http://eprints.soton.ac.uk/id/eprint/27498
ISSN: 0954-7894
PURE UUID: 0820e37e-7449-418b-a0b7-4a8b72d85a67
ORCID for P.M. Lackie: ORCID iD orcid.org/0000-0001-7138-3764

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Date deposited: 27 Apr 2006
Last modified: 16 Mar 2024 02:45

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Contributors

Author: J. Xu
Author: R.C. Benyon
Author: S.H. Leir
Author: S. Zhang
Author: S.T. Holgate
Author: P.M. Lackie ORCID iD

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