Accumulation of elafin in actinic elastosis of sun-damaged skin: elafin binds to elastin and prevents elastolytic degradation.
Elafin has a primary structure with two functional domains; a transglutaminase substrate domain at the N-terminus and a protease inhibitor domain at the C-terminus. Elafin expression has so far been reported only for epithelial tissues. Accumulation of elafin was immunohistochemically detected in the actinic elastosis of sun-damaged skin. Exposure of normal skin to UVA induced elafin expression that colocalized with elastic fibers. Incubation of synthetic transglutaminase substrate domain of elafin and elastin molecules in the presence of tissue transglutaminase in vitro resulted in the formation of a higher molecular complex on SDS-PAGE. Elafin expression was not detected in normal cultured skin fibroblasts, but was induced by UVA irradiation at both messenger RNA and protein levels. When radiolabeled insoluble elastin was incubated with recombinant full-length elafin and tissue transglutaminase, insoluble elastin became more resistant to neutrophil elastase digestion. These results indicate that (1) dermal fibroblasts potentially express elafin on UV irradiation, (2) UV-mediated elafin interacts with elastin, and (3) the elafin-elastin complex protects elastic fibers from elastolytic degradation, leading to the accumulation of elastic fibers in the actinic elastosis of sun-damaged skin. The transglutaminase substrate moiety of elafin plays an important role in anchoring elafin at its proper sites of action during UV-induced aging processes.
Muto
Jun
J
Department of Dermatology, National Defense Medical College, Tokorozawa, Saitama, Japan. dgdxp445@ybb.ne.jp
Kuroda
Kei
K
Wachi
Hiroshi
H
Hirose
Shigehisa
S
Tajima
Shingo
S
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003432:Cross-Linking Reagents / Q000378:metabolism; D020405:Dermis / Q000378:metabolism* / Q000473:pathology*; D053492:Elafin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004548:Elasticity; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D015595:Skin Aging / Q000473:pathology / Q000502:physiology*; D012995:Solubility; D013472:Sunlight / Q000009:adverse effects; D014333:Tropoelastin / Q000737:chemistry / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects
D003432:Cross-Linking Reagents; D053492:Elafin; D053583:Interleukin-1beta; C506806:PI3 protein, human; D012333:RNA, Messenger; D014333:Tropoelastin; D019272:Leukocyte Elastase