BAMBI is expressed in endothelial cells and is regulated by lysosomal/autolysosomal degradation

PloS One
Sandhya XavierDetlef Schlondorff

Abstract

BAMBI (BMP and Activin Membrane Bound Inhibitor) is considered to influence TGFβ 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. 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. TGFβ 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 3' untranslated sequence of both the human and murine BAMBI gene. BAMBI protein turnover was studied in HUVECs with BAMBI overexpression using a lentiviral system. Serum starvation as an inducer of autophagy caused marked BAMBI degradation, which could be totally prevented by inhibition of lysosomal and autolysosomal degradation with bafilomycin, and partially by inhibition of autophagy with 3-methyladenine, but not ...Continue Reading

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Methods Mentioned

BETA
confocal microscopy
biopsies
genotyping
biopsy
lipidation
PCR
transfection

Related Concepts

BAMBI protein, human
Bambi protein, mouse
Programmed Cell Death, Type II
Kidney
Lysosomes
Cell Surface Proteins
Mice, Inbred C57BL
Mice, Knockout
3' Untranslated Regions
Vascular Endothelial Cells

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