Premium
Topical treatment with a cathepsin G inhibitor, β‐keto‐phosphonic acid, blocks ultraviolet irradiation‐induced basement membrane damage in hairless mouse skin
Author(s) -
Kusumaningrum Novi,
Oh JangHee,
Lee Dong Hun,
Shin ChangYup,
Jang JeeHee,
Kim Yeon Kyung,
Chung Jin Ho
Publication year - 2019
Publication title -
photodermatology, photoimmunology and photomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.736
H-Index - 60
eISSN - 1600-0781
pISSN - 0905-4383
DOI - 10.1111/phpp.12438
Subject(s) - hairless , basement membrane , chemistry , wrinkle , lamina lucida , dermoepidermal junction , hemidesmosome , laminin , microbiology and biotechnology , biophysics , biochemistry , biology , dermis , extracellular matrix , anatomy , genetics
Summary Background Ultraviolet light ( UV ) exposure contributes various effects to skin including damage of the basement membrane. Cathepsin G ( CTSG ) belongs to serine protease family, and its upregulation is involved in wrinkle formation by chronic UV irradiation. However, the effect of CTSG on the basement membrane damage in skin remains unclear. Purpose To investigate the effects of topical treatment with a CTSG inhibitor, β‐keto‐phosphonic acid ( KPA ), on basement membrane damage in chronically UV ‐irradiated hairless mouse skin. Methods The dorsal skin of hairless mice was exposed to UV three times per week for 8 weeks. KPA was applied immediately after each session of UV irradiation. The basement membrane components, CTSG expression, and neutrophil infiltration were analyzed by immunofluorescence staining. The basement membrane structures were visualized by transmission electron microscope. CTSG and MMP ‐13 protein levels were analyzed by Western blotting. Assessment of wrinkle formation was examined using a skin replica assay. Results β‐keto‐phosphonic acid prevented UV irradiation‐induced decrease in type VII collagen, laminin 332, and perlecan at the basement membrane zone and prevented UV ‐induced breakage of lamina densa and UV ‐induced shortening of hemidesmosome. KPA prevented UV ‐induced CTSG and MMP ‐13 expressions in chronically UV ‐irradiated hairless mice. Increase in neutrophil infiltration by UV irradiation and UV ‐induced wrinkle formation was also prevented by KPA . Conclusion Our present study showed the possible involvement of CTSG in UV ‐induced basement membrane damage in skin through topical treatment with a CTSG inhibitor, KPA . Thus, inhibition of CTSG may be a useful strategy for the prevention of UV ‐induced basement membrane damage and photoaging.