# CONNECTIVE TISSUE ACTIVATION IN RHEUMATIC DISEASES

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1989 · $212,185

## Abstract

The key hypothesis of this proposal holds that the connective
tissue activation process contributes to the events of
inflammation, influencing both the reparative (proliferative) and
destructive components.  The long term objectives will be:

1)  to define the molecular characteristics of two potent
initiators of connective tissue activation, connective tissue
activating peptides III and V, (CTAP-III and CTAP-V),

2)  to assess the relevance of CTAP-III and CTAP-V to the
inflammatory process and rheumatic diseases, and

3)  to define the mechanisms by which these CTAPs initiate and
sustain connective tissue activation, and to define their
pathogenetic roles in inflammation.

Molecular characterization of the mediators CTAP III and V will be
accomplished by protein fractionation guided by relevant bioassays
and detailed characterization of the amino acid sequence and
carbohydrate composition of the agonists.  Structural studies of
CTAP-IlI will concentrate on the significance of its isoelectric
point microheterogeneity and glycosylation; studies of CTAP-V will
concentrate on primary structure.  This is crucial to design of
competitive molecules and development of additional tactics for
detailed study of these agents in clinical contexts.
Immunostaining procedures and computer assisted image analysis will
permit localization of CTAP-III and V in normal and pathologic
tissues.  Immunobinding and molecular biologic studies will define
local formation of these growth factors.  ELISA measurements of
CTAP-III and V plasma levels will be correlated with rheumatic
disease activity and the efficacy of drug interventions.
Development of recombinant CTAP molecules and synthetic peptide
fragments of both native and novel configuration offers an
opportunity to develop new tactics to influence specific key sites
in the inflammatory process.

It will be important to define in greater detail the mechanism of
action of CTAP mediators with focus on receptor studies,
chemotaxis, collagenase formation and mechanisms controlling the
biosynthesis and secretion of CTAP mediators.  The ultimate goal
of these studies is the development of agents or procedures capable
of favorably modifying the inflammatory process in man.  This
includes suppressing the process (as in rheumatoid arthritis), and
enhancing aspects of it (as in wound healing).

## Key facts

- **NIH application ID:** 3154724
- **Project number:** 5R01AR010728-23
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** C WILLIAM CASTOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $212,185
- **Award type:** 5
- **Project period:** 1978-02-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154724

## Citation

> US National Institutes of Health, RePORTER application 3154724, CONNECTIVE TISSUE ACTIVATION IN RHEUMATIC DISEASES (5R01AR010728-23). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154724. Licensed CC0.

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