Bone morphogenetic proteins protect pulmonary microvascular endothelial cells from apoptosis by upregulating α-B-crystallin.
OBJECTIVE
To investigate the role of bone morphogenetic proteins (BMPs) on α-B-crystallin (CRYAB) expression and its physiological consequences on endothelial cells (ECs).


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.
From the UMR_S 956; Univ Paris 06 (UPMC); Institut National de la Santé et de la Recherche Médicale (INSERM), F-75013, Paris (M.C., M.E., O.P., S.M., F.D., K.M., S.N., F.S.); ICAN Institute for Cardiometabolism and Nutrition, Paris, France (M.E., O.P., S.M., F.D., S.N., F.S.); and UMR_S 999; INSERM; Univ Paris-Sud; LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (N.G.).
Mariana
M
Ciumas
Mélanie
M
Eyries
Odette
O
Poirier
Svetlana
S
Maugenre
France
F
Dierick
Natalia
N
Gambaryan
Kevin
K
Montagne
Sophie
S
Nadaud
Florent
F
Soubrier
D030301:Activin Receptors, Type II / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism / Q000494:pharmacology; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism / Q000494:pharmacology; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D065627:Familial Primary Pulmonary Hypertension; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000378:metabolism / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000098:blood supply*; D051379:Mice; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism*
C525809:BMP4 protein, human; C525819:BMP7 protein, human; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D034741:RNA, Small Interfering; D038203:alpha-Crystallin B Chain; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II
ACVRL1 protein, human; BMPR2 protein, human; Id1 protein, human; RNA, small interfering; Smad proteins; anoxia