Selective proteolysis by matrix metalloproteinases of photo-oxidised dermal extracellular matrix proteins
| Autor: | Neil K. Gibbs, Rachel E.B. Watson, Christopher E.M. Griffiths, Sarah A. Hibbert, Michael J. Sherratt |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteases Photoageing Ultraviolet Rays Proteolysis Matrix metalloproteinase Fibrillins Extracellular matrix 03 medical and health sciences 0302 clinical medicine Fibrillin Microfibrils medicine Humans Ultraviolet radiation (UVR) Skin biology medicine.diagnostic_test integumentary system Chemistry Fibrillin microfibrils Reactive oxygen species (ROS) Cell Biology Fibroblasts Gel electrophoresis Matrix Metalloproteinases Cell biology Fibronectins Skin Aging Fibronectin 030104 developmental biology Matrix metalloproteinase (MMP) 030220 oncology & carcinogenesis Atomic force microscopy (AFM) Microfibrils biology.protein Microfibril Reactive Oxygen Species Fibrillin |
| Zdroj: | Hibbert, S, Watson, R, Griffiths, C, Gibbs, N & Sherratt, M 2019, ' Selective proteolysis by matrix metalloproteinases of photo-oxidised dermal extracellular matrix proteins ', Cell Signal, vol. 54, pp. 191-199 . https://doi.org/10.1016/j.cellsig.2018.11.024 |
| DOI: | 10.1016/j.cellsig.2018.11.024 |
| Popis: | Photodamage in chronically sun-exposed skin manifests clinically as deep wrinkles and histologically as extensive remodelling of the dermal extracellular matrix (ECM) and in particular, the elastic fibre system. We have shown previously that loss of fibrillin microfibrils, a key elastic fibre component, is a hallmark of early photodamage and that these ECM assemblies are susceptible in vitro to physiologically attainable doses of ultraviolet radiation (UVR). Here, we test the hypotheses that UVR-mediated photo-oxidation is the primary driver of fibrillin microfibril and fibronectin degradation and that prior UVR exposure will enhance the subsequent proteolytic activity of UVR-upregulated matrix metalloproteinases (MMPs). We confirmed that UVB (280-315 nm) irradiation in vitro induced structural changes to both fibrillin microfibrils and fibronectin and these changes were largely reactive oxygen species (ROS)-driven, with increased ROS lifetime (D2O) enhancing protein damage and depleted O2 conditions abrogating it. Furthermore, we show that although exposure to UVR alone increased microfibril structural heterogeneity, exposure to purified MMPs (1, −3, −7 and − 9) alone had minimal effect on microfibril bead-to-bead periodicity; however, microfibril suspensions exposed to UVR and then MMPs were more structurally homogenous. In contrast, the susceptibly of fibronectin to proteases was unaffected by prior UVR exposure. These observations suggest that both direct photon absorption and indirect production of ROS are important mediators of ECM remodelling in photodamage. We also show that fibrillin microfibrils are relatively resistant to proteolysis by MMPs −1, −3, −7 and − 9 but that these MMPs may selectively remove damaged microfibril assemblies. These latter observations have implications for predicting the mechanisms of tissue remodelling and targeted repair. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|