# MODULATION OF KERATINOCYTE GROWTH AND SPECIALIZATION

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1991 · $178,603

## Abstract

The long term objective of the proposed studies is to understand the
underlying mechanisms controlling epidermal cell function.  The hypothesis
is that the fatty acid composition of basal cell membrane phospholipids
controls membrane fluidity.  Altered membrane fluidity would alter the
dynamics of membrane protein receptor activity, resulting in abnormal cell
function.  Biological membranes consist of a lipid bilayer composed of
phospholipids with fatty acids in the 1 and 2 carbon position.  Linoleic
acid (18:2, n-6) and arachidonic acid (20:4) are essential, and are derived
from the diet.  Many membrane bound proteins are enzymes and proteins
involved in signal transduction and their function is known to be
controlled by cell membrane fluidity (viscosity).  Benign skin diseases are
characterized by hyperproliferation and abnormal differentiation,
postulated to result from abnormal signal transduction mechanisms.  One
such disease, psoriasis, has an abnormal fatty acid membrane profile, and
is characterized by second messenger and signaling abnormalities.  An in
vitro technic using no serum results in the extremely rapid growth of
keratinocytes which do not differentiate.  These cell are extremely EFA
deficient.  Using this in vitro system studies are proposed to define the
effect of cell membrane fluidity on human keratinocytes which do not
differentiate.  These cell are extremely EFA deficient.  Using this in
vitro system studies are proposed to define the effect of cell membrane
fluidity on human keratinocyte growth and second messenger signaling
activities.  The aims are first, to determine if marked changes occur in
other key membrane lipids of these cells (sterols, sphingolipids).  Second,
protocols for restoring in vivo ratio of the fatty acids to the cells will
be developed.  Third, quantitation of the fluidity of the membranes of
normal, EFA deficient, and partially fatty acid restored cells will be done
using Electron Spin Resonance Spectroscopy and a number of spin labeled
probes.  Fourth, second messenger systems and signaling mechanisms of EFA
deficient and restored cells will be studied.  These are:  expression of
EGF receptor and associated tyrosine kinase activity; cAMP and cGMP
systems; phospholipase A2 and C systems, all of which are abnormally
expressed in psoriasis.  The technologies of in vitro cell growth, HPLC
analysis, TLC, ESR spectroscopy, PAGE, receptor affinity determinations and
enzyme assays will be used.  Recent studies using ESR spectroscopy
demonstrate that altered cell membrane fatty acid content does alter the
viscosity of the keratinocyte membrane.  Medium changes designed to alter
cell fatty acid profiles were successful in altering the fatty acid content
of the cultures, changes accompanied by demonstrated changes in membrane
fluidity.  Thus new evidence supports the hypothesis that basal cell fatty
acid composition controls membrane fluidity.  The studies described in this
application propose to study the me...

## Key facts

- **NIH application ID:** 3155383
- **Project number:** 5R01AR026009-11
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** Cynthia L Marcelo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $178,603
- **Award type:** 5
- **Project period:** 1979-07-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155383

## Citation

> US National Institutes of Health, RePORTER application 3155383, MODULATION OF KERATINOCYTE GROWTH AND SPECIALIZATION (5R01AR026009-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155383. Licensed CC0.

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