# NATURE OF MAMMALIAN CUTANEOUS PERMEABILITY BARRIER

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1987 · $192,916

## Abstract

The stratum corneum of terrestrial mammals is now accepted to be a
heterogeneous structure of protein-enriched intercellular domains.  This
"two-compartment model" explains many phenomena of importance for cutaneous
barrier function.  The intercellular lipids of the stratum corneum appear
to derive from the secretion of a distinctive organelle, the epidermal
lamellar body, which possesses a distinctive profile of lipids, and a
select group of hydrolytic enzymes.  With the establishment of a
lifted-culture model, where human keratinocytes elaborate lamellar bodies
when grown at an air/medium interface, and a new isolation technique for
lamellar bodies, we will now study the lamellar body secretory system.
Specifically, we will use pharmacologic agents in the lifted culture
system, to separately assess the contents, site of synthesis, assembly,
kinetics, translocation, targeting, and exocytosis of lamellar bodies.
Finally, the intercellular transformation of secreted lamellar body
contents into hydrophobic lamellae in the stratum corneum interstices will
be studied using a new lipid-retaining, rapid-freeze protocol.  A second
major goal of this proposal is to determine how environmental factors and
dietary fatty acids influence barrier structure, function, and
composition.  Third, we well determine how barrier requirements regulate
epidermal lipid biosynthesis, and which lipids and enzymes are specifically
affected.  For these studies we will use a series of short-term (SDS,
acetone-treatment) and long-term (essential fatty acid deficiency,
retinoid-treatment) models of barrier disruption in hairless mice.  Fourth,
we will study water flux as a regulatory signal to lipid biosynthesis.
Finally, the ability of specific lipids to influence barrier function will
be studied in model systems that should also shed light on the molecular
basis for stratum corneum permeability.  These studies should provide new
strategies for the regulation of cutaneous barrier function that could
result in novel forms of therapy for burn wounds, and improved delivery of
topical drugs.

## Key facts

- **NIH application ID:** 3155017
- **Project number:** 2R01AR019098-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** Peter M Elias
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $192,916
- **Award type:** 2
- **Project period:** 1979-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155017

## Citation

> US National Institutes of Health, RePORTER application 3155017, NATURE OF MAMMALIAN CUTANEOUS PERMEABILITY BARRIER (2R01AR019098-12). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155017. Licensed CC0.

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