title: Inhibitory Smad transcription factors protect arterial endothelial cells from apoptosis induced by BMP4.
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.
authors.affiliation: Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kiyono
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
mesh_terms: 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
chemical_list: 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