c-Kit Pathway Influences Scleroderma Development
Much research into scleroderma aims to improve our understanding of the biological processes involved in its development and progression. Research carried out at the Royal Free Hospital in London by Dr Richard Stratton and his colleagues looked at a process known as the c-Kit pathway. They found that a cell signalling molecule called stem cell factor (SCF), which is believed to be involved in the development of scleroderma, interacts with a small group of cells that have c-Kit receptors, and might therefore be a therapeutic target in the future.
SCF is mainly released by collagen-producing fibroblast cells and epidermal skin cells. Previous research suggests SCF plays a role in the development of fibrosis in early systemic sclerosis. SCF interacts with c-Kit, a receptor on the surface of a type of white blood cell. This interaction can cause itching, which can relate to disease activity, and altered skin pigmentation, which may be due to altered SCF/c-Kit signalling affecting the cells that produce pigment.
The Royal Free study measured the activity of SCF/c-Kit in systemic sclerosis. SCF RNA levels were higher in epithelial cells and lung fibroblasts of people with scleroderma than in healthy people. SCF levels in the plasma and fluid were either lower in scleroderma patients or the same as in healthy people. A small proportion of fibroblast cells had c-Kit proteins and if SCF is important in the development of scleroderma, it is thought that SCF may act locally on these cells.
Yamamoto T et al. Expression of stem cell factor in the lesional skin of systemic sclerosis. Dermatology 1998;197:109-14