New research reveals a critical cellular signaling pathway that is responsible for generating excess connective tissue in multiple organs, similar to what is seen in human patients with scleroderma.
The study, published by Cell Press in the February issue of the journal Developmental Cell , also reveals an intriguing but unexpected regulatory role for a tumor suppressor gene in fibrotic disease.
Platelet derived growth factors (PDGF) regulate the proliferation, survival, migration and differentiation of cells and play a critical role during embryonic development. However, the consequences of excess PDGF signaling are not very well understood.
"Aberrant PDGF signaling has been implicated in diverse fibrotic conditions where connective tissue cells called fibroblasts proliferate and deposit excessive connective tissue, leading to progressive scarring and organ dysfunction," says senior study author, Dr. Philippe Soriano from the Mount Sinai School of Medicine in New York."For example, human scleroderma patients, who characteristically exhibit widespread fibrosis, possess antibodies that activate PDGF receptors."
Dr. Soriano and Dr. Lorin E. Olson, who conducted this work initially at the Fred Hutchinson Cancer Research Center in Seattle and then pursued it at Mount Sinai, developed a mouse model in which they could selectively activate the PDGF receptor alpha (PDGFR?) during embryonic development and in adult animals.