# MATRIX PROTEINASES IN CONNECTIVE TISSUE DISEASES

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 1994 · $160,060

## Abstract

Human development, growth and health critically depends on tissue
remodeling and the exquisite balance between the synthesis and
degradation of connective tissues.  At times, inconsistencies in tissue
remodeling result in developmental anomalies and devastating connective
tissue diseases that can affect the skin, blood vessels, bone and
cartilage of the joints.  A number of these diseases are known to be
genetic and inherited and are the result of structural mutations in the
genes that encode collagen, the most abundant proteins of the body.  In
many acquired type of connective tissue diseases such as osteoarthritis
and rheumatoid arthritis, the underlying causes have not been identified.
However, increasing evidence suggests a critical role for the connective
tissued degrading enzymes or matrix metalloproteinases, growth factors
and inflammatory cytokines in the pathogenesis of arthritic joint
destruction.  We hypothesize that tissue remodeling is largely controlled
by the expression of matrix metalloproteinases.  Accordingly, in this
proposal, we will study the regulation of expression of matrix
metalloproteinases at a genetic level, using mutational analysis and
transient gene transfection of cultured cells.  In particular, we plan
to study the activation and inhibition of tissue collagenase and
stromelysin genes by cytokines and growth factors including IL-1beta,
TNFalpha and FGF, and hormones such as glucocorticoids and retinoic acid.

Recently, we and others have shown that several proto-oncogenes are
involved in the expression and regulation of matrix metalloproteinase
genes.  We therefore also propose to systematically study a wide variety
of different oncoprotein and transcription factors for their effects on
collagenase ad stromelysin gene expression and for their role in the
regulation induced by cytokines, growth factors and glucocorticoid and
retinoid hormones.  As long term goals, research applications of these
studies are targeted for the regulation of matrix metalloproteinase genes
in vivo, and the treatment and prevention of major connective tissue
disorders and diseases such as arthritis.

## Key facts

- **NIH application ID:** 2199162
- **Project number:** 2R01HD024442-07
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **SAM.gov UEI:** M6K6NTJ2MNE5
- **Principal Investigator:** MARKKU T KURKINEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $160,060
- **Award type:** 2
- **Project period:** 1988-08-01 → 1997-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199162

## Citation

> US National Institutes of Health, RePORTER application 2199162, MATRIX PROTEINASES IN CONNECTIVE TISSUE DISEASES (2R01HD024442-07). Retrieved via MORVS 2026-10-26 from https://api.morvs.ai/grant/nih/2199162. Licensed CC0.

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