Grant: Operating Grant

Millions of Canadians suffer from chronic diseases in which one of the main features is the destruction of body organs and excessive scarring of the tissue (fibrosis). Thousands of these people die each year from fibrotic diseases: in fact, it has been estimated that half of all deaths in the developing world occur as a direct consequence of fibrosis of body organs. Fibroblasts are cells embedded in the skin and walls of the organs: these are not only able to produce scar tissue, but also to contract and thereby modulate tissue stiffness. Changes in ion concentration including calcium have marked effects on fibroblast function. We want to investigate if these ion changes have a direct influence on the tissue strain and organ wall composition, and if correcting abnormal calcium levels in or around fibroblasts have a beneficial effect on chronic disease. We know that fibroblasts demonstrate very interesting calcium responses when they are stimulated by growth factors. So we want to look at the relationship between changes in calcium inside the cells and production of the scar tissue proteins (gene expression). We are able to get human fibroblasts from lung tissues removed during surgical procedures. We can then separate out the fibroblasts and study them using our special microscopes (confocal, laser-illuminated, fluorimetric microscope) in order to see the changes in calcium under various experimental conditions. We can also look at how they express genes. We will therefore look at that gene expression under conditions in which calcium levels are changed. Our work will shed light on how tissue fibrosis happens, and may identify a new way to treat many fibrotic diseases, including pulmonary fibrosis and emphysema.