Abstract
In skin, the basement membrane at the dermal-epidermal junction (DEJ-BM) is an important structure that tightly binds the epidermis to the dermis, and acts as a permeability barrier that controls exchange of macromolecules. Repair of the DEJ-BM during wound healing is important for restoration of skin functional properties after wounding. Here, we used a CO2 laser to perform partial thickness wounds in human volunteers, and directly compared wound repair in healthy young and aged individuals, focusing on the DEJ-BM. Our results show that the DEJ-BM is restored within four weeks after partial thickness wounds in young adults. We identified laminin-γ2 as preferred substrate for keratinocytes during reepithelialization of partial thickness human wounds. Laminin-γ2 is expressed continuously by migrating keratinocytes during reepithelialization, whereas collagen IV and collagen VII are deposited after wound closure. In contrast, our study shows that the DEJ-BM restoration following wounding is deficient in elderly individuals. Specifically, COL7A2 was barely increased during wound repair in aged skin and, as a result, the DEJ-BM in elderly skin was not restored and showed abnormal structure. Our data suggest that ameliorating the quality of the DEJ-BM restoration is a promising therapeutic approach to improve the quality of repaired skin in the elderly.
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Abbreviations
- AF:
-
Anchoring fibrils
- BM:
-
Basement membrane
- CO2 :
-
Carbon dioxide
- DEJ-BM:
-
Dermal-epidermal junction basement membrane
- HD:
-
Hemidesmosome
- TEM:
-
Transmission electron microscopy
- IHC:
-
Immunohistochemistry
- LCM:
-
Laser capture microdissection
- LD:
-
Lamina densa
- LL:
-
Lamina lucida
- qPCR:
-
Quantitative real-time RT-PCR
- SEM:
-
Standard error of the mean
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Acknowledgements
We thank Suzan Rehbine, LPN, for her help with volunteer recruitment and tissue collection, Dorothy Sorenson (Microscopy and Image-analysis Laboratory) and for her help with operating the electron microscope. This research was supported by the University of Michigan Dermatology Department research fund, and K01 grant AR059678 from the NIH/NIAMS (to LR). The Microscopy and Image-analysis Laboratory is a multiuser imaging facility supported by the University of Michigan.
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Fisher, G., Rittié, L. Restoration of the basement membrane after wounding: a hallmark of young human skin altered with aging. J. Cell Commun. Signal. 12, 401–411 (2018). https://doi.org/10.1007/s12079-017-0417-3
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DOI: https://doi.org/10.1007/s12079-017-0417-3