# REVERSE GENETIC ANALYSIS IN TISSUE INJURY

> **NIH NIH K11** · OCHSNER CLINIC FOUNDATION · 1994 · $87,475

## Abstract

Tissue responds to damage with an early reflux of polymorphonuclear cells
and subsequent influx of monocytes/macrophages into the wound area.
Mitogenic factors derived from macrophages have not only been recognized
as essential to normal wound-healing, but have also been implicated in the
fibrosis that can occur with chronic inflammation. Transforming growth
factor-beta (TGFbeta), a mitogenic factor that plays a strong role in
tissue regulation, has been shown to be secreted by platelets and activated
macrophages.

Although TGFbeta is thought to play its strong regulatory role primarily
through effects on other growth factors and the extracellular matrix
(resulting in its overall increase), the in vivo role of TGFbeta is poorly
understood. The goal of this project is to study the effects of TGFbeta in
vivo by preparing a mutant TGFbeta that is not only inactive, but also will
inactivate wild-type TGFbeta when it forms a heterodimer with the mutant.
This takes advantage of the fact that TGFbeta is translated as a
prepro-form and is processed to an active protein.

The dominant TGFbeta mutant gene will be linked to a promoter that is only
active in activated macrophages (visna virus long terminal repeat), and
this construct will be used to develop a transgenic model. It is the
eventual goal of the principal investigator to examine the role of
macrophage-derived TGFbeta in chronic inflammation, primarily in the lung.
With this transgenic model, various experimental methods could be used to
produce lung damage, providing information not only on the role of
macrophage-derived TGFbeta in chronic inflammation but also on its role in
normal wound-healing.

## Key facts

- **NIH application ID:** 2194377
- **Project number:** 5K11HD000880-04
- **Recipient organization:** OCHSNER CLINIC FOUNDATION
- **SAM.gov UEI:** GBPMHQM2SRL3
- **Principal Investigator:** JANET E LARSON
- **Activity code:** K11 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $87,475
- **Award type:** 5
- **Project period:** 1991-03-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194377

## Citation

> US National Institutes of Health, RePORTER application 2194377, REVERSE GENETIC ANALYSIS IN TISSUE INJURY (5K11HD000880-04). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/2194377. Licensed CC0.

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