Inhibitory Smad transcription factors protect arterial endothelial cells from apoptosis induced by BMP4.
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.
Kiyono
M
M
Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
Shibuya
M
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001158:Arteries / Q000166:cytology / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051785:Smad Proteins / Q000378:metabolism*; D014162:Transfection; D014680:Veins / Q000166:cytology / Q000378:metabolism
C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D051785:Smad Proteins