# VITAMIN A AND KERATINIZATION IN HUMAN EPITHELIAL CELLS

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1992 · $309,355

## Abstract

Our objective is to elucidate the mechanisms underlying growth and
differentiation in human epithelial tissues.  The human epidermis has been
chosen as a model system, since we can cultivate these cells under
conditions where differentiative properties, including stratification and
keratinization, are retained.  The major epidermal proteins are keratins.
Basal keratinocytes express K14 (50 kd) and K5 (58 kd).  As cells undergo
terminal differentiation, they downregulate K5 and K14 mRNAs and induce
expression of K1 and K10.  This switch may enhance filament bundling, an
early indication of differentiation.  In squamous cell carcinomas, K1 and
K10 is reduced, and K6 and K16 appear in suprabasal cells.  These keratins
are not normally expressed, but are induced transiently during wound-
healing.  We have shown that both normal and abnormal differentiation are
controlled negatively by vitamin A.  When elevated to ~10X higher than
physiological, synthesis of all suprabasal keratins are downregulated.
SQCC cells are more sensitive to retinoic acid (RA) than normal cells, and
differentiation can be completely blocked with RA treatment of SQCC lines.
Prerequisite to understanding how retinoids control differentiation and why
they are useful therapeutically is to elucidate the biochemical behavior of
basal cells, i.e. the precursors of the differentiating cells.  Central to
this study is investigating the sequences and factors controlling basal
keratinocyte genes.  We have isolated the functional K5 and K14 genes.
Using a reporter or tagged K14 gene, coupled with (1) transfection of
cultured keratinocytes, and (2) transgenic mouse technology, we have begun
to elucidate mechanisms underlying K14/K5 gene expression.  Parallel to
these studies, we will explore events leading to Ra-mediated inhibition of
differentiation.  We will examine the kinetics and level of regulation of
each Ra-induced change.  Of particular interest will be whether K5 and K14
and their keratinocyte transcription factors are regulated by retinoids.
Finally, we will (1) examine the role of the steroid hormone-like retinoic
acid receptors (RARs) in controlling the RA response, and (2) investigate
whether these receptors are involved in the induction of expression of
autocrine regulators, including TGF-alpha and TGF-betas, which may act in
conjunction with vitamin A to control growth and differentiation.  A
knowledge of the factors controlling this balance is a prerequisite to
understanding how this equilibrium goes awry in the course of human
diseases, e.g. psoriasis and basal- and squamous- cell carcinomas.  The
global aim of this proposal is to coordinate the molecular biology of human
differentiation with the application of this research to medicine.

## Key facts

- **NIH application ID:** 3156080
- **Project number:** 5R01AR031737-10
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** ELAINE FUCHS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $309,355
- **Award type:** 5
- **Project period:** 1983-01-01 → 1996-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156080

## Citation

> US National Institutes of Health, RePORTER application 3156080, VITAMIN A AND KERATINIZATION IN HUMAN EPITHELIAL CELLS (5R01AR031737-10). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156080. Licensed CC0.

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