# MECHANISM OF COLLAGEN ACCUMULATION IN DERMAL FIBROSES

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1988 · $89,244

## Abstract

Human skin fibroblasts in tissue culture have provided a useful tool by
which to study connective tissue alterations in various disease processes.
In this application, we are proposing studies designed to delineate
molecular mechanisms which regulate collagen accumulation and synthesis by
skin fibroblasts.  For this purpose, fibroblast cultures established from
patients with various forms of dermal fibrotic conditions (keloids,
scleroderma, familial cutaneous collagenoma, connective tissue nevus of the
collagen type), and which are collagen over-producers will be compared to
control cells.  Also, fibroblast cultures subjected to all-trans-retinoic
acid treatment will be studied, since retinoic acid suppresses collagen
production.  Utilizing these two models of collagen production, we will
first establish the correlation between Type I procollagen biosynthesis
rates and the abundance of type I collagen specific mRNA levels, using
Northern blot and dot blot hybridization techniques.  If altered collagen
mRNA levels are found, the rate of nuclear transcription of the type I
collagen gene will be measured and the turnover of collagen mRNA
transcripts will be determined by pulse-chase experiments.  Should altered
transcriptional rates be found, studies of DNASE I hypersensitivity and
level of gene methylation will be initiated, using specific restriction
endonucleases.  Finally, the type I collagen gene copy number will be
determined in fibroblast cultures established from patients with conditions
of dermal fibrosis.  Using these experimental approaches, it is hoped that
specific levels of regulation of collagen gene expression can be
determined.  This knowledge will aid us in understanding fibrotic disease
processes and may enable us to develop pharmacologic means by which to
minimize the debilitating effects of these diseases.

## Key facts

- **NIH application ID:** 3157144
- **Project number:** 5R01AR035297-05
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** JOUNI UITTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $89,244
- **Award type:** 5
- **Project period:** 1987-01-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157144

## Citation

> US National Institutes of Health, RePORTER application 3157144, MECHANISM OF COLLAGEN ACCUMULATION IN DERMAL FIBROSES (5R01AR035297-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157144. Licensed CC0.

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