scholarly journals Epigenetic control of hypoxia inducible factor-1α-dependent expression of placental growth factor in hypoxic conditions

Epigenetics ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. 600-610 ◽  
Author(s):  
Laura Tudisco ◽  
Floriana Della Ragione ◽  
Valeria Tarallo ◽  
Ivana Apicella ◽  
Maurizio D'Esposito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Placental Growth Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Epigenetic Control ◽  
Hypoxic Conditions

scholarly journals Placenta growth factor augments endothelin-1 and endothelin-B receptor expression via hypoxia-inducible factor-1α

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 856-865 ◽  
Author(s):  
Nitin Patel ◽  
Caryn S. Gonsalves ◽  
Punam Malik ◽  
Vijay K. Kalra
Keyword(s):  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Receptor Expression ◽  
Placenta Growth Factor ◽  
Promoter Regions ◽  
Endothelin B Receptor ◽  
Endothelin 1 ◽  
Hypoxia Inducible Factor 1Α ◽  
Endothelin B ◽  
Potent Vasoconstrictor

Abstract Pulmonary hypertension (PHT) develops in sickle cell disease (SCD) and is associated with high mortality. We previously showed that erythroid cells produce placenta growth factor (PlGF), which activates monocytes to induce proinflammatory cytochemokines, contributing to the baseline inflammation and severity in SCD. In this study, we observed that PlGF increased expression of endothelin-1 (ET-1) and endothelin-B receptor (ET-BR) from human pulmonary microvascular endothelial cells (HPMVECs) and monocytes, respectively. PlGF-mediated ET-1 and ET-BR expression occurred via activation of PI-3 kinase, reactive oxygen species and hypoxia inducible factor-1α (HIF-1α). PlGF increased binding of HIF-1α to the ET-1 and ET-BR promoters; this effect was abrogated with mutation of hypoxia response elements in the promoter regions and HIF-1α siRNA and confirmed by chromatin immunoprecipitation analysis. Furthermore, PlGF-mediated ET-1 release from HPMVECs and ET-BR expression in monocytes creates a PlGF–ET-1–ET-BR loop, leading to increased expression of MCP-1 and IL-8. Our studies show that PlGF-induced expression of the potent vasoconstrictor ET-1 and its cognate ET-BR receptor occur via activation of HIF-1α, independent of hypoxia. PlGF levels are intrinsically elevated from the increased red cell turnover in SCD and in other chronic anemia (eg, thalassemia) and may contribute to inflammation and PHT seen in these diseases.

scholarly journals Hypoxia-inducible factor 1α induces osteo/odontoblast differentiation of human dental pulp stem cells via Wnt/β-catenin transcriptional cofactor BCL9

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shion Orikasa ◽  
Nobuyuki Kawashima ◽  
Kento Tazawa ◽  
Kentaro Hashimoto ◽  
Keisuke Sunada-Nara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Dental Pulp Stem Cells ◽  
Pulp Tissue ◽  
Odontoblast Differentiation ◽  
Hypoxia Inducible Factor 1Α ◽  
Hypoxic Conditions

AbstractAccelerated dental pulp mineralization is a common complication in avulsed/luxated teeth, although the mechanisms underlying this remain unclear. We hypothesized that hypoxia due to vascular severance may induce osteo/odontoblast differentiation of dental pulp stem cells (DPSCs). This study examined the role of B-cell CLL/lymphoma 9 (BCL9), which is downstream of hypoxia-inducible factor 1α (HIF1α) and a Wnt/β-catenin transcriptional cofactor, in the osteo/odontoblastic differentiation of human DPSCs (hDPSCs) under hypoxic conditions. hDPSCs were isolated from extracted healthy wisdom teeth. Hypoxic conditions and HIF1α overexpression induced significant upregulation of mRNAs for osteo/odontoblast markers (RUNX2, ALP, OC), BCL9, and Wnt/β-catenin signaling target genes (AXIN2, TCF1) in hDPSCs. Overexpression and suppression of BCL9 in hDPSCs up- and downregulated, respectively, the mRNAs for AXIN2, TCF1, and the osteo/odontoblast markers. Hypoxic-cultured mouse pulp tissue explants showed the promotion of HIF1α, BCL9, and β-catenin expression and BCL9-β-catenin co-localization. In addition, BCL9 formed a complex with β-catenin in hDPSCs in vitro. This study demonstrated that hypoxia/HIF1α-induced osteo/odontoblast differentiation of hDPSCs was partially dependent on Wnt/β-catenin signaling, where BCL9 acted as a key mediator between HIF1α and Wnt/β-catenin signaling. These findings may reveal part of the mechanisms of dental pulp mineralization after traumatic dental injury.

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