Molecular basis of proliferative diseases associated with BMP receptor mutations

BMP signaling is transduced by BMP receptors （e.g., BMPR2), which are located at cell membrane. Mutations of BMP receptor genes are known to cause pulmonary hypertension, congenital heart defects, and juvenile polyposis syndrome. We investigated molecular mechanism, by which BMP receptor mutations develop ccell-proliferative diseases, using BMPR2-deficient mice and fibroblast cells isolated from the mice. We found that BMPR2-deficient fibroblast cells promoted proliferation of epithelial cells. Also, suppression of BMP signaling augmented TNF-induced NK-kB activation. These results suggest that increased inflammatory response may play an important role in the pathogenesis of the diseases caused by the BMP receptor mutations