Hypothesis: The pulmonary myofibroblast plays a central role in the development of lung fibrosis. The local environment, associated with cyclical stretch and expression of TGF-beta, favors the use of signal transduction pathways that lead to the development of cells with properties and gene expression patterns of both muscle cells and fibroblasts. The increased matrix synthesis of these cells decreases the compliance of the tissue, leading to mechanotransduction events tht further increase synthesis of matrix. Figure 1. Postulated sequence of development of progressive fibrosis in vitro, wherein only fibroblasts, matrix, TGF-beta and physical forces are allowed to operate. We hypothesize that the unique mechanical properties of the lung permits (in the presence of TGF-beta) progression of stress-sensitive fibroblasts to myofibroblasts, and increases matrix production that increases stress.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL067671-02
Application #
6616354
Study Section
Special Emphasis Panel (ZHL1)
Project Start
2002-08-01
Project End
2003-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
2
Fiscal Year
2002
Total Cost
$288,699
Indirect Cost
Name
National Jewish Health
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206
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