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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
Inhibitory Smad transcription factors protect arterial endothelial cells from apoptosis induced by BMP4
1Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
Abstract:
Arterial endothelial cells (EC) at the adult stage differ from capillary and venous EC in terms of resistance to stress; however, the molecular basis of this resistance is not clear. Here, we found that arterial EC are highly resistant to bone morphogenetic protein (BMP)4-dependent apoptosis, whereas capillary and venous EC are not. The expression of inhibitory Smads (I-Smads) in arterial EC was well correlated with the resistance to this apoptosis. After the knockdown of I-Smad expression by short interfering RNA, the resistant arterial EC became sensitive to BMP4. In contrast, the ectopic expression of I-Smads in BMP4-sensitive cells suppressed BMP4-induced apoptosis. Furthermore, intravenous administration of BMP4 into mice caused hemorrhage of capillary EC in brain and lung. These results strongly suggest that BMP4/I-Smads are a novel regulator for the stability of vascular EC.
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