# BIOGENESIS AND FUNCTION OF CONNECTIVE TISSUE PROTEINS

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1989 · $207,634

## Abstract

Although we know a good deal about the structure and function of many
structural macromolecules, there is very little understanding of the manner
in which the production of such macromolecules is regulated.  An
appropriate balance between synthesis and degradation is crucial in
connective tissues because the tolerance, consistent with normal function,
for matrix components is small.  This is due, in part, to the slow
metabolic turnover of connective tissue proteins in the adult and to the
resulting tendency of changes to become cumulative with time.  Since we now
know that structural macromolecules, in addition to their
mechanical-protective roles, also function in sensitive cell-matrix
interactions to instruct cellular activity during tissue development and
repair, the need for careful regulation of matrix production becomes even
more clearcut.

The proposed experiments focus on the regulation of type I collagen
synthesis by fibroblasts in culture and in cell-free translation systems
because this protein is a major constituent of most connective tissues and
because pathways for its synthesis and secretion have been elucidated.
Model regulatory processes that act at the level of transcription (viral
transformation and tumor promoters) and at the level of translation
(feedback regulation by procollagen-derived fragments) will be examined.
Levels of protein synthesis as well as messenger RNA levels (assessed by
cell-free translation and hybridization using cloned cDNA probes for types
I and III collagens) will be determined.  Fibroblasts from patients with
heritable disorders of connective tissues in which the metabolic defect
appears to result in a quantitative, rather than in a qualitative, change
in collagen synthesis in vitro will be studied since such cells may
highlight regulatory mechanisms that would otherwise be difficult to
discern.

In another facet of this work, analysis of the effects of heparin on smooth
muscle cells will be pursued.  The inductive effects of heparin serve as an
example of the way in which an extracellular modulator may influence the
phenotype of an important vascular cell and may provide an understanding of
some of the events leading to atherosclerosis.

In sum, these experiments are designed to cover the broad spectrum of
regulatory controls that a cell is likely to have at its disposal in
modulating extracellular matrix production.

## Key facts

- **NIH application ID:** 3154730
- **Project number:** 5R01AR011248-23
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** PAUL BORNSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $207,634
- **Award type:** 5
- **Project period:** 1975-02-01 → 1990-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154730

## Citation

> US National Institutes of Health, RePORTER application 3154730, BIOGENESIS AND FUNCTION OF CONNECTIVE TISSUE PROTEINS (5R01AR011248-23). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3154730. Licensed CC0.

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