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Title: Mechanistic studies on the human epidermis
Author: Raj, N.
ISNI:       0000 0004 7231 2257
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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This thesis is an effort to study the concepts of skin barrier function in relation to skin physiology and biochemistry. The study focused on anatomical differences, effects of photoaging, the sensitivity of skin and pigmentation differences. The most photoexposed area of the skin is the face, so the study was designed to evaluate the factors responsible for barrier function in the facial stratum corneum. Firstly, stratum corneum (SC) protein estimated using a colorimetric assay was compared to the non-destructive Squamescan® method. The study found a good correlation between the two methods for forearm and cheek SC protein. The anatomical differences in relation to filaggrin (filaggrin) degrading proteases bleomycin hydrolase (BH) and calpain-1 (C-1) together with the pyrrolidone carboxylic acid (PCA) were analysed from tape strips of cheek, forearm and leg. The results showed the highest activity of filaggrin degrading proteases in the tapes 4-12. Interestingly, the lowest PCA level was quantified from the cheek, in spite of higher protease activity compared to the other two sites. The next study aimed at understanding the variations of these biomarkers in relation to pigmentation and photodamage. The results showed that the photodamage is associated with a significant decrease in SC barrier function. The study also investigated the role of ethnic differences in SC biochemistry and demonstrated that subjects with the highest level of photodamage had increased levels of plasmin activity and reduced cell maturation. Finally, the last study focused on sensitive skin. Biomarkers were measured in samples taken from the cheek. BH and PCA were found to be lowest in sensitive subjects. The lower corneocyte maturity in the sensitive group was well correlated with the lower transglutaminase activity. This thesis highlights the need to improve NMF levels and the activities of late stage filaggrin degrading enzymes together with a proper differentiation of corneocytes in order to improve the SC barrier. In conclusion, the thesis reports new methods of quantification of the filaggrin degrading enzyme activity, plasmin activity and PCA levels from tape strips. New data have also been generated for variation of these biomarkers in different anatomical sites, ethnicities and skin conditions generated which will provide more information about the molecular biochemistry of SC.
Supervisor: Munday, M. ; Gibbons, S. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available