# MODULATION OF KERATINOCYTE GROWTH AND SPECIALIZATION

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1988 · $137,645

## Abstract

Our objective is to attain an understanding of how epidermal keratinocyte
growth and differentiation is regulated.  Studies of epidermis taken from
human subjects with skin disease can suggest areas of research on the
control of epidermal cell function.  In the skin disease psoriasis the
epidermis is hyperproliferative, shows abnormal differentiation, and
altered arachidonic acid and eicosanoid metabolism.  Arachidonate is bound
to cell membrane phospholipids.  Two enzymes, phospholipase A2 and C, act
on the phospholipids to release free arachidonate which is further
transformed into an number of eicosanoids.  1,2 diacylglyceride (DAG),
which is formed via the phospholipase C pathway, is biologically active;
the cellular content of DAG may be controlled by DAG lipase activity.  The
available data allow the postulates that 1) the activity of phospholipase
A2 and C, and of 1,2, DAG lipase are abnormal in psoriatic epidermis.  2)
that the activity of these three enzymes and the cellular content of 1,2,
DAG can control epidermal growth and differentiation.  To test these
hypotheses it is proposed 1) to determine the activity of phospholipase A2
and C, and of 1,2 DAG lipase in normal, uninvolved and lesional psoriasis,
2) To determine the activity of phospholipase A2, of phospholipase C, and
of 1,2,DAG lipase in neonatal mouse keratinocyte cultures whose
proliferative rate and keratin synthesis are altered by growth in a number
of epidermal growth regulators.  These are the glucocorticoids,
desoximetasone and triamcinolone acetonide; two vitamin A analogues;
cholera toxin and 8-BrcAMP, which augment cellular cAMP activity; the
mitogen and tumor promoter TPA (tetradecanoy 1phorobol acetate); low
calcium growth medium.  Human epidermal biopsies will be assayed, and the
functional studies will be done using primary neonatal mouse keratinocyte
cultures.  In vitro enzyme assays, thin layer chromatograph, high
performandce liquid chromatography and radioimmune assays will be done.  In
continuing studies, monoclonal antibodies to keratin proteins will be used
to study the keratin differentiation process.  The studies will determine
how arachidonic acid metabolism via two different pathways are involved in
epidermal keratinocyte function.

## Key facts

- **NIH application ID:** 3155381
- **Project number:** 5R01AR026009-08
- **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:** 1988
- **Award amount:** $137,645
- **Award type:** 5
- **Project period:** 1979-07-01 → 1989-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155381

## Citation

> US National Institutes of Health, RePORTER application 3155381, MODULATION OF KERATINOCYTE GROWTH AND SPECIALIZATION (5R01AR026009-08). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155381. Licensed CC0.

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