UVA irradiation stimulates the synthesis of various matrix-metalloproteinases (MMPs) in cultured human fibroblasts.
UVA irradiation leads to photoaging including clinical features such as wrinkle formation, reduced recoil capacity and blister formation of the skin. Besides synthesis of the extracellular matrix, its regulated degradation by various matrix-metalloproteinases (MMPs) determines the amount and the composition of the extracellular matrix within the dermis and the basement membrane of the dermo-epidermal junction. In this study we therefore ascertained whether UV irradiation could modulate the synthesis of MMPs with substrate specificities for dermal (collagen I, III, V) and basement membrane compounds (collagen IV, VII, proteoglycans, laminin) and whether synthesis of the counteracting tissue inhibitor of metalloproteinases (TIMP-1) was also affected. Following UVA irradiation specific mRNAs of MMPs 1, 2 and 3 were induced concomitantly up to 5-fold compared to mock irradiated controls. In contrast, TIMP-1 mRNA levels remained unaltered. Immunoprecipitation indicated that after UVA irradiation synthesis and secretion of MMPs 1, 2 and 3 into the supernatant increased. Taken together, our data show that UVA irradiation coordinately induced MMPs 1, 2 and 3 implying similar mechanisms in their regulatory pathways, while TIMP-1 synthesis was not altered. Hence, unbalanced synthesis of MMPs potentially contributes to the dissolution of dermal and basement membrane compounds finally leading to blister formation and cutaneous photoaging.
Herrmann
G
G
Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.
Wlaschek
M
M
Lange
T S
TS
Prenzel
K
K
Goerz
G
G
Scharffetter-Kochanek
K
K
D000199:Actins / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D018093:Gelatinases / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000528:radiation effects; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D019714:Tissue Inhibitor of Metalloproteinases; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000199:Actins; D006023:Glycoproteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1