Cross-linking of the dermo-epidermal junction of skin regenerating from keratinocyte autografts - Anchoring fibrils are a target for tissue transglutaminase

被引:89
作者
Raghunath, M
Hopfner, B
Aeschlimann, D
Luthi, U
Meuli, M
Altermatt, S
Gobet, R
BrucknerTuderman, L
Steinmann, B
机构
[1] UNIV MUNSTER,DEPT DERMATOL,D-48149 MUNSTER,GERMANY
[2] UNIV ZURICH,CHILDRENS HOSP,PEDIAT BURN CTR,ZURICH,SWITZERLAND
[3] UNIV ZURICH,CENT LAB ELECTRON MICROSCOPY,ZURICH,SWITZERLAND
[4] UNIV ZURICH,DIV METAB & MOLEC DIS,ZURICH,SWITZERLAND
[5] UNIV WISCONSIN,DEPT MED,MADISON,WI 53706
[6] UNIV MUNSTER,DEPT DERMATOL,D-4400 MUNSTER,GERMANY
[7] UNIV MUNSTER,INST PHYSIOL CHEM & PATHOBIOCHEM,D-4400 MUNSTER,GERMANY
关键词
wound healing; transglutaminase; burns; skin; collagen VII;
D O I
10.1172/JCI118901
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Since transglutaminases create covalent gamma-glutamyl-epsilon-lysine cross-links between extracellular matrix proteins they are prime candidates for stabilizing tissue during wound healing. Therefore, we studied the temporo-spatial expression of transglutaminase activity in skin regenerating from cultured epithelial autografts in severely burned children by the specific incorporation of monodansylcadaverine into cryostat sections from skin biopsies obtained between 5 d to 17 mo after grafting. The dansyl label was subsequently immunolocalized in the epidermis, dermal connective tissue, and along the basement membrane, Incubation of cryosections of normal and regenerating skin with purified tissue transglutaminase confirmed the dermo-epidermal junction and the papillary dermis as targets for this enzyme and revealed that in regenerating skin transamidation of the basement membrane zone was completed only 4-5 mo after grafting. Immunoelectron microscopy revealed that three distinct regions on the central portion of anchoring fibrils were positive for monodansylcadaverine in normal skin which were negative during the initial phase of de novo formation of anchoring fibrils in regenerating skin. Biochemically, we identified collagen VII as potential substrate for tissue transglutaminase. Thus, tissue transglutaminase appears to play an important role not only in cross-linking of the papillary dermis but also of the dermo-epidermal junction in particular.
引用
收藏
页码:1174 / 1184
页数:11
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