# BIOCHEMICAL AND VASCULAR ALTERATIONS IN SCLERODERMA

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1991 · $191,767

## Abstract

Scleroderma (PSS) is a serious disease of unknown cause characterized by
excessive accumulation of collagen and other connective tissue components
in skin and internal organs.  There are three outstanding features involved
in the pathogenesis of PSS:  a) excessive collagen deposition; b) vascular
abnormalities and c) alterations in humoral and cellular immunity.

We will continue to investigate the role of each of these components
employing state-of-the-art methods currently being used in our
laboratories.  We previously showed that PSS fibroblasts display increased
biosynthesis of collagen and elevated levels of Types I and III procollagen
mRNAs.  We will extend these studies to examine the mechanisms responsible
for these alterations employing in vitro transcription assays and
determination of mRNA stability.  In addition, we will examine the
transcriptional regulation of collagen gene expression by transfection of
chimeric alphal(I) procollagen-CAT gene and minigene constructs containing
various deletions in the promoter and first intron regions of the gene.
Transfection of these constructs into normal and PSS fibroblasts will allow
to determine the elements within the gene responsible for normal regulation
of expression and their interaction with transcriptional factors.  These
studies will yield information that may permit the identification of the
levels of regulation of collagen gene expression that are abnormal in PSS.

To investigate the role of immunologic alterations, we will continue our
studies on the modulation of fibroblast collagen gene expression by gamma-
interferon (gamma-IFN) and transforming growth factor-beta(TGFbeta) and
will identify alterations in their production by PSS T cell subpopulations
employing Northern hybridizations nad polymerase chain reaction
amplification of reverse transcriptase-generated cDNAs.  The mechanisms
responsible for modulation of collagen synthesis by gamma-IFN and TGFbeta
will be studied utilizing in vitro transcription and transient transfection
experiments and by the identification of gamma-IFN and TGBbeta-induced
transcriptional factors.

To study the mechanisms involved in PSS vascular alterations we will
examine the effect of gamma-IFN, TGFbeta and T cell products on
microvascular endothelial cells.  It is expected that this comprehensive
approach will give further insight into the pathogenesis and possible
treatment of this incurable disease.

## Key facts

- **NIH application ID:** 3155053
- **Project number:** 5R01AR019616-15
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** SERGIO A JIMENEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $191,767
- **Award type:** 5
- **Project period:** 1987-09-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155053

## Citation

> US National Institutes of Health, RePORTER application 3155053, BIOCHEMICAL AND VASCULAR ALTERATIONS IN SCLERODERMA (5R01AR019616-15). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155053. Licensed CC0.

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