
pmid: 24072698
Objective— To investigate the role of bone morphogenetic proteins (BMPs) on α-B-crystallin ( CRYAB ) expression and its physiological consequences on endothelial cells (ECs). Approach and Results— We report that the gene encoding for the small heat shock protein, CRYAB , is a transcriptional target of the BMP signaling pathway. We demonstrate that CRYAB expression is upregulated strongly by BMPs in an EC line and in human lung microvascular ECs and human umbilical vein ECs. We show that BMP signals through the BMPR2-ALK1 pathway to upregulate CRYAB expression through a transcriptional indirect mechanism involving Id1. We observed that the known antiapoptotic effect of the BMPs is, in part, because of the upregulation of CRYAB expression in EC. We also show that cryab is downregulated in vivo, in a mouse model of pulmonary arterial hypertension induced by chronic hypoxia where the BMP pathway is downregulated. Conclusions— We demonstrate a cross-talk between BMPs and CRYAB and a major effect of this regulatory interaction on resistance to apoptosis.
Activin Receptors, Type II, Bone Morphogenetic Protein 7, Hypertension, Pulmonary, Endothelial Cells, Apoptosis, Bone Morphogenetic Protein 4, Bone Morphogenetic Protein Receptors, Type II, Up-Regulation, [SDV] Life Sciences [q-bio], Growth Differentiation Factors, Disease Models, Animal, Mice, Bone Morphogenetic Proteins, Growth Differentiation Factor 2, Human Umbilical Vein Endothelial Cells, Animals, Humans, Familial Primary Pulmonary Hypertension, RNA, Small Interfering, Lung, Signal Transduction
Activin Receptors, Type II, Bone Morphogenetic Protein 7, Hypertension, Pulmonary, Endothelial Cells, Apoptosis, Bone Morphogenetic Protein 4, Bone Morphogenetic Protein Receptors, Type II, Up-Regulation, [SDV] Life Sciences [q-bio], Growth Differentiation Factors, Disease Models, Animal, Mice, Bone Morphogenetic Proteins, Growth Differentiation Factor 2, Human Umbilical Vein Endothelial Cells, Animals, Humans, Familial Primary Pulmonary Hypertension, RNA, Small Interfering, Lung, Signal Transduction
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