Beauty biology map

Skin barrier function

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

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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 FLG — high confidence
  • Skin barrier function associated with CERS3 — high confidence
  • Skin barrier function associated with ABCA12 — high confidence
  • Skin barrier function associated with TGM1 — high confidence
  • Skin barrier function associated with CASP14 — medium confidence
  • Skin barrier function associated with AQP3 — medium confidence
  • Skin barrier function associated with PNPLA1 — medium confidence
  • FLG participates in Formation of the cornified envelope — high confidence
  • CERS3 participates in Formation of the cornified envelope — high confidence
  • ABCA12 participates in Formation of the cornified envelope — high confidence
  • TGM1 participates in Formation of the cornified envelope — high confidence
  • CASP14 participates in Formation of the cornified envelope — medium confidence
  • AQP3 participates in Formation of the cornified envelope — medium confidence
  • PNPLA1 participates in Formation of the cornified envelope — medium confidence
  • FLG participates in Sphingolipid metabolism — high confidence
  • CERS3 participates in Sphingolipid metabolism — high confidence
  • ABCA12 participates in Sphingolipid metabolism — high confidence
  • TGM1 participates in Sphingolipid metabolism — high confidence
  • CASP14 participates in Sphingolipid metabolism — medium confidence
  • AQP3 participates in Sphingolipid metabolism — medium confidence
  • PNPLA1 participates in Sphingolipid metabolism — medium confidence
  • FLG participates in Cholesterol biosynthesis — medium confidence
  • CERS3 participates in Cholesterol biosynthesis — medium confidence
  • ABCA12 participates in Cholesterol biosynthesis — medium confidence
  • TGM1 participates in Cholesterol biosynthesis — medium confidence
  • CASP14 participates in Cholesterol biosynthesis — medium confidence
  • AQP3 participates in Cholesterol biosynthesis — medium confidence
  • PNPLA1 participates in Cholesterol biosynthesis — medium confidence
  • FLG participates in Passive transport by aquaporins — medium confidence
  • CERS3 participates in Passive transport by aquaporins — medium confidence
  • ABCA12 participates in Passive transport by aquaporins — medium confidence
  • TGM1 participates in Passive transport by aquaporins — medium confidence
  • CASP14 participates in Passive transport by aquaporins — medium confidence
  • AQP3 participates in Passive transport by aquaporins — medium confidence
  • PNPLA1 participates in Passive transport by aquaporins — medium confidence
  • Formation of the cornified envelope associated with Epidermal barrier formation — high confidence
  • Sphingolipid metabolism associated with Epidermal barrier formation — high confidence
  • Cholesterol biosynthesis associated with Epidermal barrier formation — medium confidence
  • Passive transport by aquaporins associated with Epidermal barrier formation — medium confidence
  • Formation of the cornified envelope associated with Stratum corneum hydration — high confidence
  • Sphingolipid metabolism associated with Stratum corneum hydration — high confidence
  • Cholesterol biosynthesis associated with Stratum corneum hydration — medium confidence
  • Passive transport by aquaporins associated with Stratum corneum hydration — medium confidence
  • Formation of the cornified envelope associated with Transepidermal water loss regulation — high confidence
  • Sphingolipid metabolism associated with Transepidermal water loss regulation — high confidence
  • Cholesterol biosynthesis associated with Transepidermal water loss regulation — medium confidence
  • Passive transport by aquaporins associated with Transepidermal water loss regulation — medium confidence
  • Formation of the cornified envelope associated with Desquamation — medium confidence
  • Sphingolipid metabolism associated with Desquamation — medium confidence
  • Cholesterol biosynthesis associated with Desquamation — medium confidence
  • Passive transport by aquaporins associated with Desquamation — medium 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 and envelope crosslinking.

    Reactome R-HSA-6809371

  • Sphingolipid metabolism

    high confidence

    and acylceramide production for the 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 .

    Reactome R-HSA-432047

Ingredients studied here

Processes

  • —
  • hydration —
  • regulation —
  • —

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.

Limitations — Review 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.

Limitations — Narrative 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.

Limitations — Short 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.

Limitations — Review 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.

Limitations — Sparse controlled evidence; mechanism partly unresolved.

HumanJournal of Cosmetic Dermatology · 2016n = 33

Allantoin in barrier-support formulations: tolerability and hydration endpoints

Reported improved hydration and reduced roughness with an allantoin-containing emollient, without isolating the ingredient.

Limitations — Multi-ingredient formulation prevents attribution; identifier not verified during curation.

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.

Limitations — Review; 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.

Limitations — Mechanistic review; largely non-topical models.

HumanInternational Journal of Cosmetic Science · 2014n = 22

Polyglutamic acid film formation and short-term skin hydration

Reported increased corneometry readings shortly after application, attributed to a hygroscopic surface film.

Limitations — Short measurement window, no long-term barrier endpoints; identifier not verified during curation.

Identifier not curated — search Europe PMCPolyglutamic acid · Hyaluronic acid
ReviewJournal of Investigative Dermatology (review) · 2012

Natural moisturising factor composition and stratum corneum hydration

Summarises filaggrin proteolysis as the source of pyrrolidone carboxylic acid and its contribution to corneocyte water binding.

Limitations — Review; does not evaluate topical sodium PCA products; identifier not verified during curation.

Identifier not curated — search Europe PMCSodium PCA · Urea · Glycerin
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.

Limitations — Biochemical 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.

Limitations — Instrumental 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.

Limitations — Immunology 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.

Limitations — Animal wound model; not equivalent to intact cosmetic use; identifier not verified.

ReviewPhytotherapy Research (review) · 2010

Centella asiatica triterpenes and wound-healing gene expression

Summarises reported collagen and matrix effects for asiaticoside and madecassoside across animal and cell models.

Limitations — Extracts vary in composition; mostly animal data; identifier not verified during curation.

ReviewBiophysical Chemistry (review) · 2010

Ectoine as a compatible solute: membrane and protein stabilisation

Summarises preferential-hydration mechanisms by which ectoine stabilises membranes and proteins under stress.

Limitations — Biophysical review, not cutaneous; identifier not verified during curation.

In-vitroJournal of Agricultural and Food Chemistry · 2010

Avenanthramides and NF-kB dependent cytokine release in keratinocyte culture

Reported reduced IL-8 release and NF-kB reporter activity in stimulated keratinocytes exposed to purified avenanthramides.

Limitations — Purified compounds at defined concentrations, unlike commercial extracts; identifier not verified during curation.

Identifier not curated — search Europe PMCAvenanthramides (colloidal oat)
In-vitroInternational Journal of Cosmetic Science · 2009

Squalane occlusivity and stratum corneum lipid compatibility

Reported reduced water loss across model membranes attributed to a compatible, non-polar occlusive film.

Limitations — Model membranes, not human skin; identifier not verified during curation.

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.

Limitations — Ex-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.

Limitations — Cell model; identifier not verified; concentration relevance unclear.

ReviewJournal of Investigative Dermatology (review) · 2008

Glycerol and aquaporin-3 mediated water transport in epidermis

Summarises evidence that AQP3 transports both water and glycerol, linking glycerol to stratum corneum hydration.

Limitations — Mechanistic review including mouse knockout data; identifier not verified during curation.

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.

Limitations — Cell model; identifier not verified during curation.

ReviewJournal of Drugs in Dermatology (review) · 2007

Colloidal oatmeal: mechanisms and clinical use in dry, itchy skin

Summarises reported anti-inflammatory activity of avenanthramides alongside the occlusive and buffering effects of the whole extract.

Limitations — Review; extract composition is variable between products; identifier not verified during curation.

Identifier not curated — search Europe PMCAvenanthramides (colloidal oat)
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.

Limitations — Manufacturer-affiliated authorship; appearance endpoints partly investigator-graded.

PMID 16029679Niacinamide
HumanJournal of Cosmetic Dermatology · 2005n = 27

Oat beta-glucan penetration and soothing endpoints in human skin

Reported improvement in dryness and itch scores, with penetration of the polysaccharide into the upper epidermis described in accompanying imaging.

Limitations — Small sample, manufacturer-supported; identifier not verified during curation.

Identifier not curated — search Europe PMCBeta-glucan · Avenanthramides (colloidal oat)
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.

Limitations — Review; 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.

Limitations — Animal 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.

Limitations — Experimental irritation model; identifier not verified during curation.

HumanSkin Pharmacology and Applied Skin Physiology · 2002n = 25

Dexpanthenol and epidermal barrier repair after experimental irritation

Reported faster recovery of transepidermal water loss after sodium lauryl sulfate irritation with dexpanthenol versus vehicle.

Limitations — Experimental irritation model rather than clinical disease; 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.

Limitations — In-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.

Limitations — In-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.

Limitations — Animal model; identifier not verified during curation.

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

Community evidence

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