bambi is expressed in endothelial cells and is regulated by lysosomalautolysosomal degradation小鹿斑比表达于内皮细胞,是由lysosomalautolysosomal退化.pdf

BAMBI Is Expressed in Endothelial Cells and Is Regulated by Lysosomal/Autolysosomal Degradation 1 1 3 1 1 1 Sandhya Xavier , Victoria Gilbert , Maria Pia Rastaldi , Stefanie Krick , Dmitrij Kollins , Anand Reddy , 1 2 1 Erwin Bottinger , Clemens D. Cohen , Detlef Schlondorff * 1 Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America, 2 Division of Nephrology and Institute of Physiology with Center of Integrative Human Physiology, University Hospital and University of Zurich, Zurich, Switzerland, 3 Renal Immunopathology Laboratory, Fondazione D’Amico per la Ricerca sulle Malattie Renali, Milan, Italy Abstract Background: BAMBI (BMP and Activin Membrane Bound Inhibitor) is considered to influence TGFb and Wnt signaling, and thereby fibrosis. Surprisingly data on cell type-specific expression of BAMBI are not available. We therefore examined the localization, gene regulation, and protein turnover of BAMBI in kidneys. Methodology/Principal Findings: By immunofluorescence microscopy and by mRNA expression, BAMBI is restricted to endothelial cells of the glomerular and some peritubular capillaries and of arteries and veins in both murine and human kidneys. TGFb upregulated mRNA of BAMBI in murine glomerular endothelial cells (mGEC). LPS did not downregulate mRNA for BAMBI in mGEC or in HUVECs. BAMBI mRNA had a half-life of only 60 minutes and was stabilized by cycloheximide, indicating post-transcriptional regulation due to AU-rich elements, which we identified in the 39 untranslated sequence of both the human and murine BAMBI gene. BAMBI protein turnover was studied in HUVECs with BAMBI overexpression