Molecular basis of proliferative diseases associated with BMP receptor mutations

BMP信号是由BMP受体（如BMPR2）转导的，BMP受体位于细胞膜上。已知BMP受体基因突变可引起肺动脉高压、先天性心脏缺陷和青少年性息肉病综合征。我们利用bmpr2缺陷小鼠和从小鼠分离的成纤维细胞，研究了BMP受体突变导致细胞增殖性疾病的分子机制。我们发现bmpr2缺失的成纤维细胞促进上皮细胞的增殖。此外，BMP信号的抑制增强了tnf诱导的NK-kB激活。这些结果提示，炎症反应的增加可能在BMP受体突变引起的疾病的发病机制中起重要作用

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