Expression of elastolytic cathepsins in human skin and their involvement in age-dependent elastin degradation
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Expression of elastolytic cathepsins in human skin and their involvement in age-dependent elastin degradation. / Panwar, Preety; Hedtke, Tobias; Heinz, Andrea; Andrault, Pierre-Marie; Hoehenwarter, Wolfgang; Granville, David J; Schmelzer, Christian E H; Brömme, Dieter.
In: B B A - General Subjects, Vol. 1864, No. 5, 129544, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Expression of elastolytic cathepsins in human skin and their involvement in age-dependent elastin degradation
AU - Panwar, Preety
AU - Hedtke, Tobias
AU - Heinz, Andrea
AU - Andrault, Pierre-Marie
AU - Hoehenwarter, Wolfgang
AU - Granville, David J
AU - Schmelzer, Christian E H
AU - Brömme, Dieter
N1 - Copyright © 2020. Published by Elsevier B.V.
PY - 2020
Y1 - 2020
N2 - BACKGROUND: Skin ageing is associated with structure-functional changes in the extracellular matrix, which is in part caused by proteolytic degradation. Since cysteine cathepsins are major matrix protein-degrading proteases, we investigated the age-dependent expression of elastolytic cathepsins K, S, and V in human skin, their in vitro impact on the integrity of the elastic fibre network, their cleavage specificities, and the release of bioactive peptides.METHODS: Cathepsin-mediated degradation of human skin elastin samples was assessed from young to very old human donors using immunohistochemical and biochemical assays, scanning electron microscopy, and mass spectrometry.RESULTS: Elastin samples derived from patients between 10 and 86 years of age were analysed and showed an age-dependent deterioration of the fibre structure from a dense network of thinner fibrils into a beaded and porous mesh. Reduced levels of cathepsins K, S, and V were observed in aged skin with a predominant epidermal expression. Cathepsin V was the most potent elastase followed by cathepsin K and S. Biomechanical analysis of degraded elastin fibres corroborated the destructive activity of cathepsins. Mass spectrometric determination of the cleavage sites in elastin revealed that all three cathepsins predominantly cleaved in hydrophobic domains. The degradation of elastin was efficiently inhibited by an ectosteric inhibitor. Furthermore, the degradation of elastin fibres resulted in the release of bioactive peptides, which have previously been associated with various pathologies.CONCLUSION: Cathepsins are powerful elastin-degrading enzymes and capable of generating a multitude of elastokines. They may represent a viable target for intervention strategies to reduce skin ageing.
AB - BACKGROUND: Skin ageing is associated with structure-functional changes in the extracellular matrix, which is in part caused by proteolytic degradation. Since cysteine cathepsins are major matrix protein-degrading proteases, we investigated the age-dependent expression of elastolytic cathepsins K, S, and V in human skin, their in vitro impact on the integrity of the elastic fibre network, their cleavage specificities, and the release of bioactive peptides.METHODS: Cathepsin-mediated degradation of human skin elastin samples was assessed from young to very old human donors using immunohistochemical and biochemical assays, scanning electron microscopy, and mass spectrometry.RESULTS: Elastin samples derived from patients between 10 and 86 years of age were analysed and showed an age-dependent deterioration of the fibre structure from a dense network of thinner fibrils into a beaded and porous mesh. Reduced levels of cathepsins K, S, and V were observed in aged skin with a predominant epidermal expression. Cathepsin V was the most potent elastase followed by cathepsin K and S. Biomechanical analysis of degraded elastin fibres corroborated the destructive activity of cathepsins. Mass spectrometric determination of the cleavage sites in elastin revealed that all three cathepsins predominantly cleaved in hydrophobic domains. The degradation of elastin was efficiently inhibited by an ectosteric inhibitor. Furthermore, the degradation of elastin fibres resulted in the release of bioactive peptides, which have previously been associated with various pathologies.CONCLUSION: Cathepsins are powerful elastin-degrading enzymes and capable of generating a multitude of elastokines. They may represent a viable target for intervention strategies to reduce skin ageing.
U2 - 10.1016/j.bbagen.2020.129544
DO - 10.1016/j.bbagen.2020.129544
M3 - Journal article
C2 - 32007579
VL - 1864
JO - B B A - General Subjects
JF - B B A - General Subjects
SN - 0304-4165
IS - 5
M1 - 129544
ER -
ID: 235474679