Our overall objectives are to define the changes in gene expression occurring in lung cells and tissues during repair of hyperoxic lung injury and to study the control mechanisms responsible for these changes.
Our specific aims are to: (1) Determine the changes in lung tissue mRNA levels for extracellular matrix components (collagen types I, III, and IV, fibronectin and laminin) and cellular proto-oncogenes(c-fos, c-myc, c-ras, and c-sis) during repair of in vivo hyperoxic lung injury. (2) Use in situ hybridization of labeled cRNA or cDNA probes onto lung tissue sections to study the temporal-spatial distribution of changes in mRNA levels for extracellular matrix components and cellular proto- oncogenes during repair of in vivo hyperoxic lung injury. (3) Determine changes in cell-specific mRNA levels for extracellular matrix components and cellular proto-oncogenes in alveolar type II cells and fibroblasts isolated from rat lung at different time points during repair of hyperoxic lung injury. (4) Determine whether changes in transcription can account for any observed changes in cellular steady-state mRNA transcript levels (for matrix genes and oncogenes) by performing """"""""run-on"""""""" transcription assays on nuclei of alveolar type II cells and fibroblasts isolated from rat lungs at different time points during repair of hyperoxic lung injury. (5) Use DNA sequences coding for the promoter region of genes for matrix components (collagen types I and III, fibronectin and laminin) and for cellular proto-oncogenes (c-fos and c-myc) to determine whether changes in promoter DNA-binding proteins in the nuclei of alveolar type II cells and fibroblasts can account for the changes in gene expression. The proposed experiments should enhance our understanding of the cellular and genetic mechanisms underlying repair of acute lung injury. The information is broadly applicable to many lung conditions involving repair of fibrosis including the Adult Respiratory Distress Syndrome.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL043256-02
Application #
3361855
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715