Attenuated kallikrein‐related peptidase activity disrupts desquamation and leads to stratum corneum thickening in human skin equivalent models

McGovern, Jacqui A.; Meinert, Christoph; Veer, Simon J. de; Hollier, Brett G.; Parker, Tony J.; Upton, Zee

doi:10.1111/bjd.14879

Cited by 26 publications

(21 citation statements)

References 61 publications

(133 reference statements)

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“…Elafin inhibits human leukocyte elastase, appearing in the granular and upper spinosum by gestational weeks 28–29. 48 It inhibited kallikrein (KLK5 and KLK7) proteolytic activity 49 and desquamation, 50 and participated in corneocyte envelope formation at terminal differentiation. 51 Reduced desquamation would be protective for PT infants, that is, until the SC is sufficiently functional.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of neonatal skin barrier adaptation reveal substantial differences compared to adult skin

et al. 2020

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Background The objective of this study was to measure skin characteristics in premature (PT), late preterm (LPT), and full-term (FT) neonates compared with adults at two times (T1, T2). Methods Skin samples of 61 neonates and 34 adults were analyzed for protein biomarkers, natural moisturizing factor (NMF), and biophysical parameters. Infant groups were: <34 weeks (PT), 34–<37 weeks (LPT), and ≥37 weeks (FT). Results Forty proteins were differentially expressed in FT infant skin, 38 in LPT infant skin, and 12 in PT infant skin compared with adult skin at T1. At T2, 40 proteins were differentially expressed in FT infants, 38 in LPT infants, and 54 in PT infants compared with adults. All proteins were increased at both times, except TMG3, S100A7, and PEBP1, and decreased in PTs at T1. The proteins are involved in filaggrin processing, protease inhibition/enzyme regulation, and antimicrobial function. Eight proteins were decreased in PT skin compared with FT skin at T1. LPT and FT proteins were generally comparable at both times. Total NMF was lower in infants than adults at T1, but higher in infants at T2. Conclusions Neonates respond to the physiological transitions at birth by upregulating processes that drive the production of lower pH of the skin and water-binding NMF components, prevent protease activity leading to desquamation, and increase the barrier antimicrobial properties. Impact Neonates respond to the transitions at birth by upregulating processes that drive the production of lower pH of the skin and NMF, prevent protease activity leading to desquamation, and increase the antimicrobial properties of the barrier. The neonatal epidermal barrier exhibits a markedly different array of protein biomarkers both shortly after birth and 2–3 months later, which are differentially expressed versus adults. The major biomarker-functional classes included filaggrin processing, protease inhibitor/enzyme regulators, antimicrobials, keratins, lipids, and cathepsins. The findings will guide improvement of infant skin care practices, particularly for the most premature infants with the ultimate goals mitigating nosocomial infection.

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Section: Discussionmentioning

confidence: 99%

Biomarkers of neonatal skin barrier adaptation reveal substantial differences compared to adult skin

et al. 2020

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“…Three‐dimensional (3D) skin equivalents are organotypic culture systems that are generated by seeding human keratinocytes onto a dermal layer with human fibroblasts . Over the last decade, 3D skin equivalents have been developed to an attractive tool for pharmacotoxicological testing of cosmetic components and clinical applications as artificial skin grafts . However, skin equivalents continuously contract during their construction and applications.…”

Section: Introductionmentioning

confidence: 99%

Construction of low contracted 3D skin equivalents by genipin cross‐linking

Meng

Shen

2018

Experimental Dermatology

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Continuous contraction of 3D skin equivalents in construction and use restricts their applications in clinical and pharmaceutical practices. So far, no effective method has been developed to inhibit such contraction. Hence, low cytotoxic cross-linkers, 1-ethyl-3-3-dimethylaminopropylcarbodiimide hydrochloride (EDC) and genipin, are investigated to reduce the contraction in this study. As found, both genipin and EDC at 0.2 and 0.4 mmol/L are nontoxic to collagen-entrapped fibroblasts and upregulate the extracellular matrix expression of fibroblasts in cross-linked collagen. Particularly, collagen cross-linking by intermediate concentrations of genipin, specifically 0.4 mmol/L, greatly reduces the contraction of 3D skin equivalents from 87% to 28% (n = 9, P < 0.05), while the collagen after EDC cross-linking at 0.4 mmol/L still presented severe contraction of 64% over a 21-day follow-up period. The inhibited contraction might relate to the increased gel stiffness and slowed collagen degradation. Moreover, the genipin cross-linking does not impair the formation of epidermal layers and improves the epidermal-dermal junction of skin equivalents as well. In this regard, genipin cross-linking might facilitate the applications of 3D skin equivalents in clinical practices and pharmacology testing.

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“…This desquamation process takes about 15‐20 days for healthy skin conditions . However, due to genetic diseases, such as ichthyosis, and abnormal skin conditions, such as aging, dryness, and acne, the keratinization process is longer and the desquamation rate (turnover rate) is slower than normal, which result in the thickening of the stratum corneum …”

Section: Introductionmentioning

confidence: 99%

Identification and validation of amino acid‐based mild exfoliating agents through a de novo screening method

Ahn¹,

Lee

Kim³

et al. 2019

J of Cosmetic Dermatology

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Background: Due to internal or external factors, the desquamation (turnover) rate of the stratum corneum slows down, resulting in skin problems. Therefore, adjusting the exfoliation rate through cosmetics is an important issue.Objective: This report aimed to develop exfoliating agents with lesser adverse effects and higher efficiency through an ex vivo screening method and in vivo turnover rate analysis of human skin.Methods: Various molecules were evaluated by the ex vivo porcine skin exfoliation method and screened for their potential as effective agents. To confirm the effect and mechanism of each agent found, the exfoliation efficiency was evaluated. Each agent was also applied to the actual human skin to determine its efficacy and side effects.Results: Despite the pH 6, carnitine and serine, which have similar or better efficiency compared to PHA, were selected. Based on the results, it was confirmed that calcium. And it is nonirritating to the human skin and increases the turnover rate (~130%). Conclusion:Amino acid-based exfoliating agents, such as carnitine and serine, were identified and verified to enhance the rate of exfoliation of the stratum corneum. It is expected that the improvement of dullness, mild acne, fine wrinkles, and pores through skin exfoliation in the field of cosmetics can be achieved safely through these agents. K E Y W O R D Samino acids, chemical peel, cosmetics, desquamation, exfoliating agent, stratum corneum

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Attenuated kallikrein‐related peptidase activity disrupts desquamation and leads to stratum corneum thickening in human skin equivalent models

Abstract: These findings demonstrate that stratum corneum thickening is due to inhibited KLK5 and KLK7 activation and a subsequent lack of corneodesmosome degradation in the HSE model epidermis.

Cited by 26 publications

References 61 publications

Biomarkers of neonatal skin barrier adaptation reveal substantial differences compared to adult skin

Biomarkers of neonatal skin barrier adaptation reveal substantial differences compared to adult skin

Construction of low contracted 3D skin equivalents by genipin cross‐linking

Identification and validation of amino acid‐based mild exfoliating agents through a de novo screening method

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