Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events.
Effects of sunlight have fascinated researchers for decades because nearly every living thing on earth is likely to be exposed to sunlight and the ultraviolet (UV) fraction of it. In addition to detrimental long-term effects such as immunosuppression and skin cancer, premature aging of the skin (photoaging) is a well-documented consequence of exposure to UVA and UVB. Photoaged skin is biochemically characterized by an overgrowth of abnormal elastic fibers in the dermis and by a dramatic decrease of distinct collagen types. Ultraviolet irradiation induces delayed UV-responsive genes, among them matrix metalloproteinases, which degrade macromolecules of the extracellular matrix, a hallmark in carcinogenesis and aging. We are interested in UVB-triggered initial events and in subsequent signaling resulting in enhanced expression of two major members of the matrix metalloproteinase family, the interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3), in human dermal fibroblasts. Especially, these skin cells play a central role in connective tissue breakdown in photoaging and as stromal cells in tumor invasion and metastasis by means of their capability to produce matrix metalloproteinases. In this review, we will focus on UVB-triggered induction of matrix metalloproteinases, the so far identified components of the UVB-modulated signal transduction pathway(s), and the UVB irradiation-associated generation of reactive oxygen species (ROS). Finally, a potentially novel aspect in UVB irradiation-mediated expression of interstitial collagenase and stromelysin-1-namely, the involvement of reactive nitrogen species (RNS)-is discussed.
Brenneisen
Peter
P
Institute for Physiological Chemistry I, Heinrich-Heine-University of Düsseldorf, 40225 Düsseldorf, Germany. Peter.Brenneisen@web.de
Sies
Helmut
H
Scharffetter-Kochanek
Karin
K
D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology* / Q000528:radiation effects; D012867:Skin / Q000528:radiation effects; D012871:Skin Diseases / Q000201:enzymology / Q000235:genetics; D014466:Ultraviolet Rays
D020782:Matrix Metalloproteinases