# MECHANISMS OF COLLAGEN ACCUMULATION IN DERMAL FIBROSES

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1990 · $102,995

## Abstract

This renewal application proposed continuation of studies towards the
overall goal of delineating the molecular mechanisms which lead to
accumulation of collagen in dermal fibroses.  This sharply focused
proposal is based on significant progress made in this project during
the previous years of support, implicating pretranslational control of
collagen gene expression in these diseases.  The studies will utilize
skin fibroblast cultures established from patients with fibrotic skin
diseases, and will specifically focus on two clinical conditions,
keloids and progressive systemic sclerosis, which serve as prototypes of
dermal fibrotic conditions.  Previous studies have concentrated on type
I and type III procollagens which are thought to be the predominant
collagens in human dermis.  Recent compelling evidence suggests that
type VI collagen is a more abundant gene product of human skin
fibroblasts than has been previously recognized.  Since type VI collagen
has been suggested to play a distinct role in collagen fibrillogenesis,
the studies proposed here will explore the role of type VI collagen in
fibrotic skin diseases in detail.  This novel approach has been made
feasible by recent cloning of human cDNAs encoding the three constituent
polypeptide chains of type VI collagen.  Finally, the role of cytokines
in fibrotic processes will be examined by evaluating the transcriptional
modulation of collagen gene expression by TGF-beta, TNF-alpha, and IL-1,
factors that have been previously shown to affect collagen gene
expression, yet the exact mechanisms and the level of interference are
currently unknown.  The specific aims of the proposal include:  1)
Elucidation of the transcriptional control elements of collagen gene
expression by utilizing transfection assays with collagen promoter/CAT
constructs; 2) Examination of cellular trans-acting regulatory elements
by detailed gel retardation and footprinting analyses; 3) Evaluation of
cis-acting control elements in collagen genes by deletion analysis of
the constructs containing putative regulatory DNA sequences linked to a
reporter (CAT) gene; 4) Spatial localization of the enhanced cellular
collagen gene expression by in situ hybridizations; 5) Modulation of
collagen gene expression in fibroblast cultures by cytokines and novel
pharmacologic means.

We expect that these experimental approaches will allow us to pinpoint
the molecular mechanism leading to accumulation of collagen in fibrotic
skin diseases.  This information may allow us to develop pharmacologic
means which could counteract these debilitating diseases by targeting
the precise levels of aberration.

## Key facts

- **NIH application ID:** 3157145
- **Project number:** 5R01AR035297-07
- **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:** 1990
- **Award amount:** $102,995
- **Award type:** 5
- **Project period:** 1987-01-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157145

## Citation

> US National Institutes of Health, RePORTER application 3157145, MECHANISMS OF COLLAGEN ACCUMULATION IN DERMAL FIBROSES (5R01AR035297-07). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3157145. Licensed CC0.

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