# VITAMIN A AND KERATINIZATION IN HUMAN EPITHELIAL CELLS

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1990 · $252,482

## Abstract

The objective is an understanding of the biochemical mechanisms that
regulate the expression of human genes during differentiation.  The human
epidermis has been chosen as a model system, since we are able to serially
cultivate these cells in vitro under conditions where many of the
differentiative properties, including stratification, are retained.  A
simple squamous epithelium, the peritoneal mesothelium, has been chosen for
purposes of comparison.  These cells can also be cultured, using a similar
system.

The major differentiation-specific proteins of the epidermis are the
keratins, a group of related proteins (M.W. 40-70kd) that form 8 nm
cytoskeletal filaments in all epithelial cells.  We have identified two
distinct multigene families encoding the keratins.  Pairs of these genes
are differentially expressed in different epithelial cells and at different
stages of keratinization.  Commitment to terminal differentiation results
in a shift in the synthesis of mRNAs encoding two pairs of smaller keratins
to the synthesis of a new pair of larger keratins (MW 56.5 and 67K).  We
have found that epidermal cells in culture will terminally differentiate if
the vitamin A in the medium is removed.  In addition to causing increased
stratification and s. corneum formation, removal of the vitamin regulates
the synthesis of the mRNAs encoding the large keratins.  In contrast,
increasing the vitamin A level leads to the expression of two keratins
(53kd and 40kd) not normally seen in epidermal cells, but made by some
cancerous cell lines and also mesothelial cells.  Recently, we constructed
a cDNA library to human mesothelial mRNA.  We have identified cDNAs
encoding the keratins of the 53kd and 40kd keratins that are positively
regulated by vitamin A.  We now propose to isolate and sequence the genes
for these proteins in order to define the regulatory sequences responsible
for the tissue-specific and vitamin A-specific expression of these genes.
We will utilize mammalian gene transfer systems to study the
transcriptional and translational regulation of these genes.  Finally,
using purified cellular receptors for the retinoids, we will investigate
whether retinoic acid and retinol act directly or indirectly to influence
the expression of these specific keratin genes.  It is our aim to elucidate
the significance of the expression of this pair of vitamin A-regulated
keratins in human epidermis and to determine the precise mechanism by which
vitamin A differentially regulates their expression.

## Key facts

- **NIH application ID:** 3156079
- **Project number:** 5R01AR031737-08
- **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:** 1990
- **Award amount:** $252,482
- **Award type:** 5
- **Project period:** 1983-01-01 → 1991-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156079

## Citation

> US National Institutes of Health, RePORTER application 3156079, VITAMIN A AND KERATINIZATION IN HUMAN EPITHELIAL CELLS (5R01AR031737-08). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156079. Licensed CC0.

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