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

作者：Ciumas Mariana; Eyries Melanie; Poirier Odette; Maugenre Svetlana; Dierick France; Gambaryan Natalia; Montagne Kevin; Nadaud Sophie; Soubrier Florent^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2013, 33(11): 2577-2584.

DOI：10.1161/ATVBAHA.113.301976

• ACVRL1 protein
• human
• anoxia
• BMPR2 protein
• human
• Id1 protein
• human
• RNA
• small interfering
• Smad proteins

Objective To investigate the role of bone morphogenetic proteins (BMPs) on -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.

• 出版日期2013-11