# NATURE OF MAMMALIAN CUTANEOUS PERMEABILITY BARRIER

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1992 · $230,078

## Abstract

Whereas prior studies have shown that the initial stages of permeability
barrier homeostasis, which require lipid synthesis, are tightly regulated,
this proposal will assess whether several subsequent stages of barrier
maintenance also are regulated processes.  First, the assembly and
secretion of the epidermal lamellar body (LB), focusing on the subcellular
site of origin of the LB and the control LB secretion by cytoskeleton and
other regulatory factors (e.g., beta-adrenergic stimuli, growth factors,
and cytokines).  Second, we will examine the regulation of extracellular
hydrolase activity, thought to transform secreted LB contents into the
intercellular bilayers that subserve the barrier.  Third, we will examine
whether specific lipids or lipid mixtures are required for barrier
homeostasis, and how this compositional profile is regulated.  In these
studies, we will employ well-characterized, hairless mouse models,
subjected to various types of barrier disruption, as well as organotypic
human keratinocyte cultures, which approach the epidermis in LB content,
lipid composition, and barrier function.  Ultrastructural, lipid
biochemical, metabolic, fluorescence and isotopic tracers,
immunocytochemical, and molecular biological approaches will be utilized.
In addition, a wide variety of pharmacologic inhibitors will be employed to
ascertain:  a) the subcellular site of LB synthesis; b) the cellular basis
for LB secretion; and c) the enzymes required for extracellular processing
of LB contents.  Interpretations will be based upon this multidisciplinary
approach applied to each of these areas to be studied.  Although our goal
is to learn as much as possible about the basic mechanisms underlying
permeability barrier homeostasis, this work has wide practical
implications.  Barrier function is lost in premature infants, extensive
burn wounds, blistering disorders, exfoliative erythrodermas, and important
dermatoses, such as psoriasis and atopic dermatitis.  These studies could
lead to new strategies to reinforce or stabilize barrier function in these
conditions.  Conversely, the range of drugs that can be delivered by the
percutaneous route is currently limited by the seeming impregnability of
the barrier.  These studies could lead to novel approaches to enhance
transdermal drug delivery, potentially allowing whole new classes of
formerly excluded compounds to access the internal environment.

## Key facts

- **NIH application ID:** 3155018
- **Project number:** 2R01AR019098-17
- **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:** 1992
- **Award amount:** $230,078
- **Award type:** 2
- **Project period:** 1979-04-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155018

## Citation

> US National Institutes of Health, RePORTER application 3155018, NATURE OF MAMMALIAN CUTANEOUS PERMEABILITY BARRIER (2R01AR019098-17). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155018. Licensed CC0.

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