Lysyl oxidase activity in human skin is increased by chronic ultraviolet radiation exposure and smoking

Langton, Abigail K.; Tsoureli-Nikita, E; Griffiths, C.E.M.; Katsambas, Andreas; Antoniou, Christina; Stratigos, A.; Sherratt, Michael J.; Watson, Rachel

doi:10.1111/bjd.14959

Cited by 10 publications

(7 citation statements)

References 11 publications

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“…Using this method, we identified that the skin of smokers is significantly stiffer than that of non‐smokers. It has previously been demonstrated that the skin of smokers has increased activity of lysyl oxidase enzymes [60,61]. Lysyl oxidases primarily drive the catalysis of cross‐links in both fibrillar collagens and elastin in the dermis [62]; however, they are also present within the epidermis of both human and mouse skin [61,63–65], where it has been suggested that they play a role in maintaining epidermal homeostasis and normal keratinocyte differentiation [66,67].…”

Section: Discussionmentioning

confidence: 99%

“…It has previously been demonstrated that the skin of smokers has increased activity of lysyl oxidase enzymes [60,61]. Lysyl oxidases primarily drive the catalysis of cross-links in both fibrillar collagens and elastin in the dermis [62]; however, they are also present within the epidermis of both human and mouse skin [61,[63][64][65], where it has been suggested that they play a role in maintaining epidermal homeostasis and normal keratinocyte differentiation [66,67]. Although the function of these enzymes in the epidermis remains to be fully elucidated, we suggest that epidermal stiffness could, at least in part, be a consequence of increased lysyl oxidase activity.…”

Section: Ak Langton Et Almentioning

confidence: 99%

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The systemic influence of chronic smoking on skin structure and mechanical function

Langton

Tsoureli-Nikita

Merrick

et al. 2020

The Journal of Pathology

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One of the major functions of human skin is to provide protection from the environment. Although we cannot entirely avoid, for example, sun exposure, it is likely that exposure to other environmental factors could affect cutaneous function. A number of studies have identified smoking as one such factor that leads to both facial wrinkle formation and a decline in skin function. In addition to the direct physical effects of tobacco smoke on skin, its inhalation has additional profound systemic effects for the smoker. The adverse effects on the respiratory and cardiovascular systems from smoking are well known. Central to the pathological changes associated with smoking is the elastic fibre, a key component of the extracellular matrices of lungs. In this study we examined the systemic effect of chronic smoking (>40 cigarettes/day; >5 years) on the histology of the cutaneous elastic fibre system, the nanostructure and mechanics of one of its key components, the fibrillin-rich microfibril, and the micromechanical stiffness of the dermis and epidermis. We show that photoprotected skin of chronic smokers exhibits significant remodelling of the elastic fibre network (both elastin and fibrillin-rich microfibrils) as compared to the skin of age-and sex-matched non-smokers. This remodelling is not associated with increased gelatinase activity (as identified by in situ zymography). Histological remodelling is accompanied by significant ultrastructural changes to extracted fibrillin-rich microfibrils. Finally, using scanning acoustic microscopy, we demonstrated that chronic smoking significantly increases the stiffness of both the dermis and the epidermis. Taken together, these data suggest an unappreciated systemic effect of chronic inhalation of tobacco smoke on the cutaneous elastic fibre network. Such changes may in part underlie the skin wrinkling and loss of skin elasticity associated with smoking.

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Section: Discussionmentioning

confidence: 99%

Section: Ak Langton Et Almentioning

confidence: 99%

The systemic influence of chronic smoking on skin structure and mechanical function

Langton

Tsoureli-Nikita

Merrick

et al. 2020

The Journal of Pathology

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“…fibronectin) and glycosaminoglycans (e.g. hyaluronic acid, dermatan sulfate) . For example, small leucine‐rich proteoglycans, such as decorin and biglycan, may play a role in regulating collagen fibril assembly, diameter, length and organization .…”

Section: Discussionmentioning

confidence: 99%

“…hyaluronic acid, dermatan sulfate). 9,10,[13][14][15][16][17]40,41 For example, small leucine-rich proteoglycans, such as decorin and biglycan, may play a role in regulating collagen fibril assembly, diameter, length and organization. 16,42 Additionally, increased mechanical tension of skin during pregnancy may play a role in preventing the formation of collagen bundles, a situation possibly analogous to impaired healing or 'spreading' of surgical wounds under high mechanical tension.…”

Section: (A) (B)mentioning

confidence: 99%

Severe disruption and disorganization of dermal collagen fibrils in early striae gravidarum

Wang

Calderone

et al. 2018

Br J Dermatol

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“…This is consistent with the ability of defensins to act as antioxidant proteins (46). Crucially, MPSC not only predicts that known photoageing biomarkers (LOX and TIMP3) will be susceptible to UVR/ROS degradation (47)(48)(49) but also highlights the potential susceptibility (TSHB, CTSB, CTSZ) and resistance (DCD, EMCN, CALM5 and APOC1) of new skin ageing biomarker proteins (Fig.1.c).…”

Section: Predicted Uvr/ros Susceptibilities Correlate Well With Publimentioning

confidence: 99%

Predicting and validating protein degradation in proteomes using deep learning

Ozols

Eckersley

Platt

et al. 2020

Preprint

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Age, disease, and exposure to environmental factors can induce tissue remodelling and alterations in protein structure and abundance. In the case of human skin, ultraviolet radiation (UVR)-induced photo-ageing has a profound effect on dermal extracellular matrix (ECM) proteins. We have previously shown that ECM proteins rich in UV-chromophore amino acids are differentially susceptible to UVR. However, this UVR-mediated mechanism alone does not explain the loss of UV-chromophore-poor assemblies such as collagen. Here, we aim to develop novel bioinformatics tools to predict the relative susceptibility of human skin proteins to not only UVR and photodynamically produced ROS but also to endogenous proteases. We test the validity of these protease cleavage site predictions against experimental datasets (both previously published and our own, derived by exposure of either purified ECM proteins or a complex cell-derived proteome, to matrix metalloproteinase [MMP]-9). Our deep Bidirectional Recurrent Neural Network (BRNN) models for cleavage site prediction in nine MMPs, four cathepsins, elastase-2, and granzyme-B perform better than existing models when validated against both simple and complex protein mixtures. We have combined our new BRNN protease cleavage prediction models with predictions of relative UVR/ROS susceptibility (based on amino acid composition) into the Manchester Proteome Susceptibility Calculator (MPSC) webapp http://www.manchesterproteome.manchester.ac.uk/#/MPSC (or http://130.88.96.141/#/MPSC). Application of the MPSC to the dermal proteome suggests that fibrillar collagens and elastic fibres will be preferentially degraded by proteases alone and by UVR/ROS and protease in combination, respectively. We also identify novel targets of oxidative damage and protease activity including dermatopontin (DPT), fibulins (EFEMP-1,-2, FBLN-1,-2,-5), defensins (DEFB1, DEFA3, DEFA1B, DEFB4B), proteases and protease inhibitors themselves (CTSA, CTSB, CTSZ, CTSD, TIMPs-1,-2,-3, SPINK6, CST6, PI3, SERPINF1, SERPINA-1,-3,-12). The MPSC webapp has the potential to identify novel protein biomarkers of tissue damage and to aid the characterisation of protease degradomics leading to improved identification of novel therapeutic targets.

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Lysyl oxidase activity in human skin is increased by chronic ultraviolet radiation exposure and smoking

Cited by 10 publications

References 11 publications

The systemic influence of chronic smoking on skin structure and mechanical function

The systemic influence of chronic smoking on skin structure and mechanical function

Severe disruption and disorganization of dermal collagen fibrils in early striae gravidarum

Predicting and validating protein degradation in proteomes using deep learning

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