bambi regulates angiogenesis and endothelial homeostasis through modulation of alternative tgfβ signaling小鹿斑比调节血管生成和血管内皮体内平衡tgfβ信号通过调制的选择.pdf

BAMBI Regulates Angiogenesis and Endothelial Homeostasis through Modulation of Alternative TGFb Signaling 1 1 1 2 2 1 Nicolas Guillot , Dmitrij Kollins , Victoria Gilbert , Sandhya Xavier , Jun Chen , Madeleine Gentle , 1 1 3 4 4 Anand Reddy , Erwin Bottinger , Rulang Jiang , Maria Pia Rastaldi , Alessandro Corbelli , Detlef Schlondorff1* 1 Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America, 2 Department of Medicine, New York Medical College, Valhalla, New York, United States of America, 3 Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America, 4 Renal Research Laboratory, Ospedale Maggior Policlinico Fondazione D’Amico per la Ricerca sulle Malattie Renali, Milan, Italy Abstract Background: BAMBI is a type I TGFb receptor antagonist, whose in vivo function remains unclear, as BAMBI2/ 2 mice lack an obvious phenotype. Methodology/Principal Findings: Identifying BAMBI’s functions requires identification of cell-specific expression of BAMBI. By immunohistology we found BAMBI expression restricted to endothelial cells and by electron microscopy BAMBI2/ 2 mice showed prominent and swollen endothelial cells in myocardial and glomerular capillaries. In endothelial cells over- expression of BAMBI reduced, whereas knock-down enhanced capillary growth and migration in response to TGFb. In vivo angiogenesis was enhanced in matrigel implants and in glomerular hypertrophy after unilateral nephrectomy in BAMBI2/ 2 compared to BAMBI+/+ mice consistent with an endothelial phenotype for BAMBI2/ 2 mice. BAMBI’s mechanism o