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Effect of retinoic acid in combination with platelet‐derived growth factor‐BB or transforming growth factor‐β on tissue inhibitor of metalloproteinases and collagenase secretion from human skin and synovial fibroblasts
Author(s) -
Bigg Heather F.,
Cawston Tim E.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199601)166:1<84::aid-jcp10>3.0.co;2-p
Subject(s) - retinoic acid , platelet derived growth factor receptor , growth factor , collagenase , transforming growth factor , platelet derived growth factor , tretinoin , fibroblast , chemistry , secretion , matrix metalloproteinase , transforming growth factor beta , retinoic acid receptor beta , microbiology and biotechnology , medicine , biology , endocrinology , retinoic acid receptor , biochemistry , receptor , in vitro , enzyme , gene
This report shows for the first time that platelet‐derived growth factor‐BB (PDGF‐BB) and transforming growth factor‐β (TGF‐β) can interact in a synergistic manner with retinoic acid to stimulate the production of tissue inhibitor of metalloproteinases (TIMP) from human skin and synovial fibroblasts. When cells are treated with 1, 10, and 100 ng/ml of either of these growth factors in combination with 10 −5 M retinoic acid, this results in a dose‐dependent synergistic induction of TIMP protein secretion which is greater than the additive effect of the agents by up to fourfold. These responses can be inhibited by the presence of specific neutralising antibodies to the growth factors, demonstrating that they are not the result of an experimental artefact such as contamination with bacterial endotoxin. The mechanisms of these synergistic responses may involve the induction of receptors for retinoic acid, PDGF, or TGF‐β or may result from synergistic effects on TIMP gene transcription. We have also found that retinoic acid potently down‐regulates PDGF‐BB‐stimulated collagenase in both types of fibroblast and that the effect of PDGF‐BB alone on collagenase secretion from skin fibrolasts is biphasic. Finally, this study reports that retinoic acid and TGF‐β do not act in an additive fashion to inhibit the production of collagenase from skin fibroblasts. © 1996 Wiley‐Liss, Inc.