Beauty biology map

Skin barrier function

The stratum corneum is a brick-and-mortar arrangement of corneocytes embedded in lamellar lipids composed chiefly of ceramides, cholesterol and free fatty acids. Filaggrin proteolysis supplies the natural moisturising factors that hold water inside corneocytes, and barrier integrity is usually measured indirectly as transepidermal water loss.

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Skin barrier functionFLGCERS3ABCA12TGM1CASP14AQP3PNPLA1Formation of the cornifie…Sphingolipid metabolismCholesterol biosynthesisPassive transport by aqua…Epidermal barrier formati…Stratum corneum hydrationTransepidermal water loss…Desquamation

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IngredientMoleculeTargetGenePathwayProcessOutcome
Text alternative for this network
  • Skin barrier function associated with FLGhigh confidence
  • Skin barrier function associated with CERS3high confidence
  • Skin barrier function associated with ABCA12high confidence
  • Skin barrier function associated with TGM1high confidence
  • Skin barrier function associated with CASP14medium confidence
  • Skin barrier function associated with AQP3medium confidence
  • Skin barrier function associated with PNPLA1medium confidence
  • FLG participates in Formation of the cornified envelopehigh confidence
  • CERS3 participates in Formation of the cornified envelopehigh confidence
  • ABCA12 participates in Formation of the cornified envelopehigh confidence
  • TGM1 participates in Formation of the cornified envelopehigh confidence
  • CASP14 participates in Formation of the cornified envelopemedium confidence
  • AQP3 participates in Formation of the cornified envelopemedium confidence
  • PNPLA1 participates in Formation of the cornified envelopemedium confidence
  • FLG participates in Sphingolipid metabolismhigh confidence
  • CERS3 participates in Sphingolipid metabolismhigh confidence
  • ABCA12 participates in Sphingolipid metabolismhigh confidence
  • TGM1 participates in Sphingolipid metabolismhigh confidence
  • CASP14 participates in Sphingolipid metabolismmedium confidence
  • AQP3 participates in Sphingolipid metabolismmedium confidence
  • PNPLA1 participates in Sphingolipid metabolismmedium confidence
  • FLG participates in Cholesterol biosynthesismedium confidence
  • CERS3 participates in Cholesterol biosynthesismedium confidence
  • ABCA12 participates in Cholesterol biosynthesismedium confidence
  • TGM1 participates in Cholesterol biosynthesismedium confidence
  • CASP14 participates in Cholesterol biosynthesismedium confidence
  • AQP3 participates in Cholesterol biosynthesismedium confidence
  • PNPLA1 participates in Cholesterol biosynthesismedium confidence
  • FLG participates in Passive transport by aquaporinsmedium confidence
  • CERS3 participates in Passive transport by aquaporinsmedium confidence
  • ABCA12 participates in Passive transport by aquaporinsmedium confidence
  • TGM1 participates in Passive transport by aquaporinsmedium confidence
  • CASP14 participates in Passive transport by aquaporinsmedium confidence
  • AQP3 participates in Passive transport by aquaporinsmedium confidence
  • PNPLA1 participates in Passive transport by aquaporinsmedium confidence
  • Formation of the cornified envelope associated with Epidermal barrier formationhigh confidence
  • Sphingolipid metabolism associated with Epidermal barrier formationhigh confidence
  • Cholesterol biosynthesis associated with Epidermal barrier formationmedium confidence
  • Passive transport by aquaporins associated with Epidermal barrier formationmedium confidence
  • Formation of the cornified envelope associated with Stratum corneum hydrationhigh confidence
  • Sphingolipid metabolism associated with Stratum corneum hydrationhigh confidence
  • Cholesterol biosynthesis associated with Stratum corneum hydrationmedium confidence
  • Passive transport by aquaporins associated with Stratum corneum hydrationmedium confidence
  • Formation of the cornified envelope associated with Transepidermal water loss regulationhigh confidence
  • Sphingolipid metabolism associated with Transepidermal water loss regulationhigh confidence
  • Cholesterol biosynthesis associated with Transepidermal water loss regulationmedium confidence
  • Passive transport by aquaporins associated with Transepidermal water loss regulationmedium confidence
  • Formation of the cornified envelope associated with Desquamationmedium confidence
  • Sphingolipid metabolism associated with Desquamationmedium confidence
  • Cholesterol biosynthesis associated with Desquamationmedium confidence
  • Passive transport by aquaporins associated with Desquamationmedium confidence

Genes & proteins

  • FLGhigh confidence

    Filaggrin

  • CERS3high confidence

    Ceramide synthase 3

  • ABCA12high confidence

    ATP binding cassette subfamily A member 12

  • TGM1high confidence

    Transglutaminase 1

  • CASP14medium confidence

    Caspase 14

  • AQP3medium confidence

    Aquaporin 3

  • PNPLA1medium confidence

    Patatin like phospholipase domain containing 1

Pathways

  • Formation of the cornified envelope

    high confidence

    Terminal keratinocyte differentiation and envelope crosslinking.

    Reactome R-HSA-6809371

  • Sphingolipid metabolism

    high confidence

    Ceramide and acylceramide production for the lipid lamellae.

    Reactome R-HSA-428157

  • Cholesterol biosynthesis

    medium confidence

    Epidermal sterol supply.

    Reactome R-HSA-191273

  • Passive transport by aquaporins

    medium confidence

    Water and glycerol movement in keratinocytes.

    Reactome R-HSA-432047

Ingredients studied here

Processes

  • Epidermal barrier formation — Stratum corneum
  • Stratum corneum hydration — Stratum corneum
  • Transepidermal water loss regulation — Stratum corneum
  • Desquamation — Stratum corneum

Research on this topic

ReviewCell Metabolism (review) · 2018

Nicotinamide and NAD precursor metabolism in human cells

Summarises the NAD salvage route in which nicotinamide is converted by NAMPT and NMNAT enzymes to NAD+, supporting redox and signalling functions.

LimitationsReview of mechanism, largely non-cutaneous; does not evaluate topical delivery.

ReviewClinical, Cosmetic and Investigational Dermatology (review) · 2018

Urea in dermatology: hydration and keratolysis by concentration

Summarises concentration-dependent behaviour of urea, humectant at low percentages and keratolytic at higher percentages.

LimitationsNarrative review without quantitative synthesis.

Randomised controlled trialJournal of Cosmetic Dermatology · 2017n = 60

Ceramide-containing moisturiser and barrier recovery in dry skin

Reported faster transepidermal water loss recovery with a ceramide-dominant formulation compared with a control emollient.

LimitationsShort duration; identifier not verified during curation.

ReviewJournal of Lipid Research (review) · 2016

Essential fatty acid deficiency and epidermal acylceramide formation

Establishes linoleate as required for omega-O-acylceramide formation, with PNPLA1 mediating the transfer step.

LimitationsReview of genetic and animal evidence; topical repletion effects less characterised.

ReviewJournal of Cosmetic Science (review) · 2016

Allantoin in topical formulations: keratolytic and soothing properties

Summarises long-standing topical use with limited modern controlled data on mechanism.

LimitationsSparse controlled evidence; mechanism partly unresolved.

ReviewInternational Journal of Cosmetic Science (review) · 2015

Squalene and squalane in skin surface lipids: oxidation and emollient behaviour

Describes squalene as readily oxidised in sebum, whereas the saturated squalane form is oxidation-resistant and functions as an emollient.

LimitationsReview; largely physicochemical rather than biological endpoints.

ReviewJournal of Biological Chemistry (review) · 2014

Hyaluronan in skin: molecular weight dependence of biological effects

Summarises how hyaluronan fragment size determines CD44 signalling outcomes, with high and low molecular weight forms behaving differently.

LimitationsMechanistic review; largely non-topical models.

In-vitroBiochemical Journal · 2011

Nicotinamide as an inhibitor of poly(ADP-ribose) polymerase activity

Characterises nicotinamide as a weak product inhibitor of PARP enzymes in cell-free assays.

LimitationsBiochemical assay; inhibitory concentrations far above physiological skin levels.

Randomised controlled trialJournal of Drugs in Dermatology · 2011n = 76

Topical hyaluronic acid formulations and skin hydration: a controlled study

Reported increased corneometry-measured hydration and reduced wrinkle depth versus baseline over 8 weeks.

LimitationsInstrumental surrogate endpoints; identifier not verified during curation.

ReviewNature Reviews Immunology (review) · 2011

Beta-glucan recognition by dectin-1 and downstream innate signalling

Establishes CLEC7A/dectin-1 as the principal receptor for beta-1,3-glucans in innate immune recognition.

LimitationsImmunology review; cosmetic topical endpoints not addressed.

AnimalJournal of Ethnopharmacology · 2010

Centella asiatica triterpenes and wound-related collagen deposition

Reported increased collagen deposition and faster wound closure in a rodent model.

LimitationsAnimal wound model; not equivalent to intact cosmetic use; identifier not verified.

In-vitroJournal of Investigative Dermatology · 2008

Filaggrin degradation products and natural moisturising factor content of the stratum corneum

Demonstrates that filaggrin proteolysis by caspase-14 and downstream enzymes generates pyrrolidone carboxylic acid and urocanic acid.

LimitationsEx-vivo/in-vitro; identifier not verified during curation.

Identifier not curated — search Europe PMCSodium PCA · Zinc PCA · Urea
In-vitroExperimental Dermatology · 2008

Zinc salts and sebaceous lipid production in vitro

Reported reduced sebocyte lipid accumulation with zinc salts, including 5-alpha reductase inhibition in cell assays.

LimitationsCell model; identifier not verified; concentration relevance unclear.

In-vitroSkin Pharmacology and Physiology · 2007

Ectoin as a protective compatible solute in keratinocyte models

Reported reduced UVA-induced signalling and membrane damage in ectoin-treated keratinocytes.

LimitationsCell model; identifier not verified during curation.

HumanDermatologic Surgery · 2005n = 50

Niacinamide: a B vitamin that improves aging facial skin appearance

Reported improvements in several appearance endpoints including fine lines and skin texture over 12 weeks of use versus vehicle.

LimitationsManufacturer-affiliated authorship; appearance endpoints partly investigator-graded.

PMID 16029679Niacinamide
ReviewJournal of Lipid Research (review) · 2003

Stratum corneum lipids and barrier function: ceramide, cholesterol and free fatty acid ratios

Establishes the approximately equimolar ceramide/cholesterol/free fatty acid composition required for competent lamellar barrier structure.

LimitationsReview; ratio requirements derived largely from animal and ex-vivo models.

Identifier not curated — search Europe PMCCeramide NP · Cholesterol · Linoleic acid
AnimalJournal of Biological Chemistry · 2002

Glycerol and aquaporin-3 in epidermal water transport

Aquaporin-3 null mice showed reduced stratum corneum glycerol and impaired hydration, restored by glycerol administration.

LimitationsAnimal knockout model; identifier not verified during curation.

Randomised controlled trialContact Dermatitis · 2002n = 25

Dexpanthenol and epidermal barrier repair after experimental irritation

Reported faster barrier recovery measured by transepidermal water loss compared with vehicle after sodium lauryl sulfate challenge.

LimitationsExperimental irritation model; identifier not verified during curation.

In-vitroJournal of Cosmetic Science · 2000

Topical niacinamide and epidermal barrier lipid synthesis in cultured keratinocytes

Reported increased ceramide and free fatty acid synthesis in keratinocyte culture after niacinamide exposure.

LimitationsIn-vitro only; concentrations may not reflect in-use exposure.

In-vitroJournal of Investigative Dermatology · 1996

Lactic acid stimulates ceramide synthesis in the epidermis

Reported increased epidermal ceramide production after lactic acid exposure in a skin model.

LimitationsIn-vitro; stereoisomer-specific effects incompletely characterised; identifier not verified.

AnimalArchives of Dermatological Research · 1996

Physiological lipid mixtures and accelerated barrier recovery

Reported that only balanced ceramide/cholesterol/fatty acid mixtures accelerated barrier recovery; incomplete mixtures delayed it.

LimitationsAnimal model; identifier not verified during curation.

Identifier not curated — search Europe PMCCholesterol · Ceramide NP · Linoleic acid

Community evidence

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