# EXTRACELLULAR MATRIX DEGRADATION IN SKIN

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 1992 · $140,922

## Abstract

Remodeling of dermal connective tissue is a feature of growth and
development and conversely, destruction of this extracellular matrix is
characteristic of neoplastic and inflammatory disorders.  Degradation of
the structural macromolecules of the dermal extracellular matrix is
mediated by a metalloproteinase family which includes interstitial
collagenase, gelatinase, and stromelysin.  These degradative enzymes are
in turn regulated by a proteinase inhibitor, Tissue Inhibitor of
MetalloProteinases or TIMP.  If the actions of the metalloproteinases and
TIMP truly play crucial roles in matrix degradation and remodeling, then
studies to determine their distribution, metabolism and regulation by
products of epithelial and dermal cells should be useful in understanding
connective tissue related disorders.

Poorly characterized factors from skin cancers and normal keratinocytes
that are capable of modulating production of metalloproteinases and TIMP
will be isolated and characterized.  Concurrent studies of specific and
well-defined cytokines relevant to skin biology (Epidermal growth factor,
Transforming growth factors a,b, Tumor necrosis factor, Interleukin-1 and
basic growth factor, Transforming growth factors a,b, Tumor necrosis
factor, Interleukin-1 and basis Fibroblast growth factor) will be used in
model systems.  The specific effects of the cytokines will be further
examined using functional, immunological, biosynthetic and mRNA
quantitation methods.

To establish the role of metalloproteinases and TIMP in matrix
degradation, the distribution of these proteins will be studied
in normal human skin and a panel of basal cell carcinomas displaying a
spectrum of connective tissue alterations.  Additionally, in situ
hybridization techniques will be employed using cDNA probes to
collagenase and TIMP to establish which cells involved in the tumor-
extracellular matrix interaction actually contain specific mRNAs. To
independently address the role of TIMP in neoplastic invasion and
metastasis, regulated expression vectors containing the TIMP sequence
will be placed in selected murine tumor lines.  Alterations in the
biological behavior of these cells when placed in a murine host should
increase our understanding of both TIMP and metalloproteinase activities
in this process.  These studies will help to identify the sites of
production of metalloproteinases and TIMP in human skin and provide
insights into the normal and abnormal physiology of connective tissue
remodeling.

## Key facts

- **NIH application ID:** 3159873
- **Project number:** 5R01AR039682-04
- **Recipient organization:** VANDERBILT UNIVERSITY
- **SAM.gov UEI:** GTNBNWXJ12D5
- **Principal Investigator:** George Putnam Stricklin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $140,922
- **Award type:** 5
- **Project period:** 1989-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159873

## Citation

> US National Institutes of Health, RePORTER application 3159873, EXTRACELLULAR MATRIX DEGRADATION IN SKIN (5R01AR039682-04). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159873. Licensed CC0.

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