FUNCTIONS OF CONNECTIVE TISSUE GROWTH FACTOR

Project: Research project

Project Details

Description

The overall objective of this proposal is to study the regulation and
function of connective tissue growth factors (CTGF) and elucidate its
autocrine/paracrine effects on airway smooth muscle cells (SMC). (CTGF, a
novel cysteine-rick peptide that exhibits platelet-derived growth factor
(PDGF) like actions, is the most abundant growth factor found in the lung
to date. Transforming growth factor beta (TGF-beta) specifically induces
the CTGF mRNA in human skin fibroblasts and vascular endothelial cells. I
have previously shown that two other growth factors, endothelin (ET) and
PDGF stimulate the migration and growth of airway SMC. These airway cells
can constitutively express ET-1 mRNA and produce ET-1. In preliminary
studies, I have shown that airway SMC also produce ad respond to CTGF. In
the present proposal, I hypothesize that growth factors such as CTGF, are
involved in the increased contractility, hyperplasia, and hypertrophy of
airway SMC that are characteristic features of bronchial asthma. SMC,
isolated from ovine trachealis muscle, will be stimulated with TGF-beta and
other cytokines and the RNA isolated and subjected to Northern analysis.
The effects of recombinant CTGF on airway SMC behavior will be studies
using receptor, proliferation, chemotaxis, and contractility assays.
Finally, immunohistochemical techniques using polyclonal CTGF antibodies
will be used to determine the localization of CTGF in sheep airway and in
situ hybridization utilized to identify cells responsible for CTGF
synthesis. Thr proposed studies will broaden our understanding of airway
smooth muscle regulation by growth factors.
StatusFinished
Effective start/end date6/1/955/31/98

Funding

  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute

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