Epidermal barrier formation and recovery in skin disorders

Segre, Julia A.

doi:10.1172/jci28521

Cited by 426 publications

(378 citation statements)

References 96 publications

(102 reference statements)

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“…Reestablishment of the barrier is a key trigger in the wound repair process, signaling the transition from increased proliferation to reestablishment of the homeostatic balance (19). Impaired epidermal barrier function is a hallmark feature of two of the most common inflammatory skin disorders, psoriasis and atopic dermatitis (39). Very recent genetic findings of commonly occurring mutations in the epidermal cornification protein filaggrin underlying susceptibility to both atopic dermatitis and asthma underscore the clinical need to understand better how barrier establishment is regulated (40).…”

Section: Discussionmentioning

confidence: 99%

Klf4 and corticosteroids activate an overlapping set of transcriptional targets to accelerate in utero epidermal barrier acquisition

Patel

Seo

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Premature infants are at an increased risk for infections and dehydration because of incomplete development of the epidermis, which attains its essential function as a barrier only during the last stages of in utero development. When a premature birth is anticipated, antenatal corticosteroids are administered to accelerate lung epithelium differentiation. One pleiotropic, but beneficial, effect of antenatal corticosteroids is acceleration of skin barrier establishment by an unknown mechanism. In mice, the transcription factor Klf4 is both necessary and sufficient, within a developmental field of competence, to establish this skin barrier, as demonstrated by targeted ablation and transgenic expression of Klf4, respectively. Here, we report that Klf4 and corticosteroid treatment coordinately accelerate barrier acquisition in vivo. Transcriptional profiling reveals that the genes regulated by corticosteroids and Klf4 during the critical window of epidermal development significantly overlap. KLF4 activates the proximal promoters of a significant subset of these genes. Dissecting the intersection of the genetic and pharmacological pathways, regulated by KLF4 and corticosteroids, respectively, leads to a mechanistic understanding of the normal process of epidermal development in utero.development ͉ transcription factor ͉ skin ͉ glucocorticoid receptor

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Section: Discussionmentioning

confidence: 99%

Klf4 and corticosteroids activate an overlapping set of transcriptional targets to accelerate in utero epidermal barrier acquisition

Patel

Seo

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Loricrin (LOR) and involucrin (IVL) are important proteins that facilitate terminal differentiation of the epidermis and formation of the skin barrier [7][8][9][10][11][12]. Human LOR is an insoluble protein initially expressed in the granular layer of the epidermis during cornification, and comprises 80% of the total protein mass of the cornified envelope (CE) [7,[13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Kim

Leung

Boguniewicz

et al. 2008

Clinical Immunology

447

206

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Atopic dermatitis (AD) is characterized by a defective skin barrier which allows increased allergen and pathogen penetration. Loricrin (LOR) and involucrin (IVL) are proteins important for skin barrier formation and integrity. In this study, we demonstrate that the gene and protein expression of LOR and IVL is significantly decreased in acute (LOR: p<0.001; IVL: p<0.001) and non-lesional (LOR: p<0.001; IVL: p<0.001) skin of AD subjects, as compared to skin from healthy subjects. Using primary keratinocytes, we further demonstrate the down-regulatory effect of IL-4 and IL-13 -which are over-expressed in the skin of AD patients -on LOR and IVL expression in keratinocytes. Additionally, skin biopsies from signal transducer and activator of transcription (STAT)-6 transgenic mice were deficient in the expression and production of LOR and IVL. This study suggests that Th2 cytokines inhibit expression of LOR and IVL through a STAT-6 dependent mechanism.

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“…The stratum corneum, the external surface layer, gives the skin its waterproofing barrier properties. This property depends on skin lipids (ceramides, cholesterol, and fatty acids) and on the mixture of natural moisturizing molecules, such as amino acids, organic acids, urea, and inorganic ions [8,9], which can absorb large amounts of water.…”

Section: Characteristic Age-related Changes Of Normal Skinmentioning

confidence: 99%

Aging Skin: Nourishing from Out-In. Lessons from Wound Healing

Corsetti

Flati

Pasini³

et al. 2015

Textbook of Aging Skin

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Skin lesion therapy, peculiarly in the elderly, cannot be isolated from understanding that the skin is an important organ consisting of different tissues. Furthermore, dermis health is fundamental for epidermis integrity, and so adequate nourishment is mandatory in maintaining skin integrity. The dermis nourishes the epidermis, and a healthy epidermis protects the dermis from the environment, so nourishing the dermis through the epidermal barrier is a technical problem yet to be resolved. This is also a consequence of the laws and regulations restricting cosmetics, which cannot have properties that pass the epidermal layer. There is higher investment in cosmetics than in the pharmaceutical industry dealing with skin therapies, because the costs of drug registration are enormous and the field is unprofitable. Still, wound healing may be seen as an opportunity to "feed" the dermis directly. It could also verify whether providing substrates could promote efficient healing and test optimal skin integrity maintenance, if not skin rejuvenation, in an ever aging population.

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Epidermal barrier formation and recovery in skin disorders

Cited by 426 publications

References 96 publications

Klf4 and corticosteroids activate an overlapping set of transcriptional targets to accelerate in utero epidermal barrier acquisition

Klf4 and corticosteroids activate an overlapping set of transcriptional targets to accelerate in utero epidermal barrier acquisition

Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

Aging Skin: Nourishing from Out-In. Lessons from Wound Healing

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