| title: | Expression of Extracellular Matrix Proteins by Human Airway Structural Cells: the Effect of Oxidative Stress and Modulation by Inflammatory Mediators |
|---|---|
| reg no: | ETF5011 |
| project type: | Estonian Science Foundation research grant |
| subject: |
1.8. Molecular Biology 3. Medical Sciences |
| status: | completed |
| institution: | Estonian Biocentre |
| head of project: | Siiri Altraja |
| duration: | 01.01.2002 - 31.12.2005 |
| description: | Chronic inflammatory diseases that involve the airways are inevitably accompanied by restructuring processes in the airway mucosa, where the qualitative and quantitative changes in extracellular matrix (ECM) impair the perspective of restitution and result in a steep and irreversible decline in lung function. This process, termed as airway remodeling, involves a significant increase in expression of certain ECM proteins (tenascin, laminins, collagens). To date, no systematic comparative studies are available on the expression and regulation of tenascin (Tn), collagens, and laminins (Lns) in human airway structural cells at the level of both protein and mRNA that approaches to simulate an inflammation generated by oxidative stress (OS) or proinflammatory mediators (cysteinyl leukotrienes, histamine), as well as to investigate the effect of anti-inflammatory cytokines such as IL-10 or antioxidants. The main goals of the project are: 1) to define the expression level of the ECM proteins, which play a significant role in the process of human airway remodeling (Tn, Ln chains alpha-2, beta-2, and gamma-2, and collagen type III), in human airway structural cell lines (bronchial epithelial cells, fibroblasts, and smooth muscle cells); 2) to clarify the changes in the expression levels of these ECM proteins during the inflammatory processes by studying the effects of OS and inflammatory mediators (cysteinyl leukotrienes, histamine) and that of the growth factor TGF-beta to the synthesis of the above mentioned ECM constituents in the airway structural cells; 3) to study the ability of antioxidants and IL-10 to modulate the expression of the ECM proteins in pre-stimulated airway structural cells with the aim to find new aspects to hinder airway remodeling in inflammatory airway diseases. As a result, more information will be obtained about the possibilities of influencing the deposition of the ECM proteins in the process of airway remodeling, as well as about the issue of reversibility of airway fibrosis that, in turn, provides opportunity for evidence-based application of new treatment strategies. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Signe Altmäe | Tartu Univ. IMCB | M.Sc student | |
| 2. | Alan Altraja | Tartu Univ. Lung Clinic | Associate Professor | |
| 3. | Siiri Altraja | Estonian Biocentre | Senior researcher | |
| 4. | Martin Kadai | Tartu Univ. IMCB | B.Sc student | |
| 5. | Janne Pullat | Estonian Biocentre | Researcher | |
| 6. | Viljo Soo | Tartu Univ. IMCB | Sen. technician | |
| 7. | Jaana Tammur | Tartu Univ. IMCB | Ph.D student | |