Thioredoxin secreted upon ultraviolet A irradiation modulates activities of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in human dermal fibroblasts

Regulation of the balance of matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) by thioredoxin (Trx) was investigated in human dermal fibroblasts. Expression and secretion of Trx and Trx reductase 1 (TR 1) was increased after ultraviolet (UV) A irradiation. A significant increase in proMMP-2 activity and a decrease of TIMP-2 activity in supernatants of UVA-irradiated fibroblasts were observed in gelatin and reverse zymography compared to non-irradiated fibroblasts. Removal of Trx or TR1 by immunoprecipitation diminished these changes in proMMP-2 activity. Incubation with 5,5'-dithio-bis-2-nitrobenzoic acid (DTNB) also suppressed these changes. Incubation with recombinant Trx or TR decreased TIMP-2 activity and increased MMP-2 activity. UVA-irradiated fibroblasts, transiently transfected with a dominant-negative mutant or wild-type Trx, showed down- or upregulation of proMMP-2 activities, respectively, without significant change of protein amount. In conclusion, thioredoxin secreted by UVA irradiation is involved in the regulation of MMP-2 and TIMP-2 activities through its redox activity in human dermal fibroblasts. (C) 2003 Elsevier Inc. All rights reserved.
Publisher
Elsevier Science Inc
Issue Date
2004
Language
ENG
Keywords

MMP-3 PROTEIN-LEVELS; B-MEDIATED INCREASE; SKIN IN-VIVO; INTERSTITIAL COLLAGENASE; MESSENGER-RNA; ESCHERICHIA-COLI; SINGLET OXYGEN; CELL INVASION; TIMP-2; ACTIVATION

Citation

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, v.423, no.1, pp.218 - 226

ISSN
0003-9861
URI
http://hdl.handle.net/10203/82411
Appears in Collection
NE-Journal Papers(저널논문)
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