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Arteriosclerosis Thrombosis and Vascular Biology
Article . 2013 . Peer-reviewed
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Bone Morphogenetic Proteins Protect Pulmonary Microvascular Endothelial Cells From Apoptosis by Upregulating α-B-Crystallin

Authors: Ciumas, Mariana; Eyries, Mélanie; Poirier, Odette; Maugenre, Svetlana; Dierick, France; Gambaryan, Natalia; Montagne, Kevin; +2 Authors

Bone Morphogenetic Proteins Protect Pulmonary Microvascular Endothelial Cells From Apoptosis by Upregulating α-B-Crystallin

Abstract

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.

Keywords

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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    21
    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
21
Top 10%
Average
Top 10%
bronze