SDF-1α Induces PDGF-B Expression and the Differentiation of Bone Marrow Cells into Pericytes

Hamdan, Randala; Zhou, Zhichao; Kleinerman, Eugenie S.

doi:10.1158/1541-7786.mcr-11-0190

Cited by 32 publications

(36 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…32 During tissue repair, SDF1 provides an endothelial cell-derived signal that promotes recruitment of bone marrowderived progenitor cells 40 and their differentiation into pericytes. 15 These events contribute to endothelial cell quiescence and vessel maturation. Hypoxia-dependent HIF1␣-mediated induction of SDF1 expression is well described in several vascular disease settings.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

BMP9 regulates endoglin-dependent chemokine responses in endothelial cells

Young

Conley

Romero

et al. 2012

Blood

View full text Add to dashboard Cite

BMP9 signaling has been implicated in hereditary hemorrhagic telangiectasia (HHT) and vascular remodeling, acting via the HHT target genes, endoglin and ALK1. This study sought to identify endothelial BMP9-regulated proteins that could affect the HHT phenotype. Gene ontology analysis of cDNA microarray data obtained after BMP9 treatment of primary human endothelial cells indicated regulation of chemokine, adhesion, and inflammation pathways. These responses included the up-regulation of the chemokine CXCL12/SDF1 and down-regulation of its receptor CXCR4. Quantitative mass spectrometry identified additional secreted proteins, including the chemokine CXCL10/IP10. RNA knockdown of endoglin and ALK1 impaired SDF1/CXCR4 regulation by BMP9. Because of the association of SDF1 with ischemia, we analyzed its expression under hypoxia in response to BMP9 in vitro, and during the response to hindlimb ischemia, in endoglin-deficient mice. BMP9 and hypoxia were additive inducers of SDF1 expression. Moreover, the data suggest that endoglin deficiency impaired SDF1 expression in endothelial cells in vivo. Our data implicate BMP9 in regulation of the SDF1/CXCR4 chemokine axis in endothelial cells and point to a role for BMP9 signaling via endoglin in a switch from an SDF1-responsive autocrine phenotype to an SDF1 nonresponsive paracrine state that represses endothelial cell migration and may promote vessel maturation. IntroductionEndoglin directly interacts with the TGF-␤ receptors, 1 including ALK1, 2 and modulates TGF-␤ and bone morphogenetic protein (BMP) signaling. 3 Mutations in either endoglin 4 or ALK1 5 increase the risk of hereditary hemorrhagic telangiectasia (HHT1 and HHT2, respectively), whose symptoms include arteriovenous malformation, tissue ischemia, and reperfusion defects. 6 The ALK1-endoglin signaling complex in endothelial cells is activated by BMP9, 7 a circulating cytokine produced in the liver reticuloendothelium 8 and endothelial cells, including those lining the mouse aorta. 9 BMP9 interacts with endoglin and ALK1 to activate signaling pathways 7 that promote endothelial cell quiescence 10 and vessel maturation. 11 Several endothelial cell-derived factors, including BMP9, are known to regulate vessel maturation via paracrine recruitment of other cell types. 12 Moreover, our recent work using nonendothelial cells implicates endoglin in the regulation of tumor neoangiogenesis via the secreted insulin-like growth factor binding protein 4. 13 Therefore, elucidation of the role of BMP9 signaling, specifically in terms of its effects on the expression of endothelial cell-secreted factors, is needed to better understand the mechanisms by which BMP9 affects vessel maturation, integrity, the vascular response to injury, and how deficiency in either endoglin or ALK1 impacts vessel integrity and cause HHT.Stromal-derived factor 1 (SDF1, CXCL12) is a chemokine that signals via the chemokine receptor, CXCR4, to modulate hypoxiainduced angiogenesis. 14 SDF1 regulates both endothelial cellmediated paracrine signaling ...

show abstract

Section: Discussionmentioning

confidence: 99%

“…14 SDF1 regulates both endothelial cellmediated paracrine signaling and endothelial cell-autonomous autocrine signaling. In endothelial cells, SDF1 is up-regulated by hypoxia 14 and promotes recruitment, vascular remodeling, and differentiation 15 of pericytes and their perivascular retention, reflecting its well known paracrine functions.…”

Section: Introductionmentioning

confidence: 99%

BMP9 regulates endoglin-dependent chemokine responses in endothelial cells

Young

Conley

Romero

et al. 2012

Blood

View full text Add to dashboard Cite

show abstract

“…Interestingly, integrins can be activated by proangiogenic chemokines such as CXCL12, triggering EC and leukocyte spreading and migration in an integrin-dependent manner [27,[57][58][59]. Moreover, CXCL12, which is upregulated by hypoxia [60], increases PDGF-B expression by ECs and promotes the differentiation and recruitment of pericytes and vascular remodeling [61], as well as myogenic differentiation [62]. Furthermore, CXCL12-induced expression of PDGF-B is in turn a potent activator of integrins [63].…”

Section: Endothelial Cells Drive and Mural Cells Polish Angiogenesismentioning

confidence: 99%

The role of endoglin in post-ischemic revascularization

et al. 2016

View full text Add to dashboard Cite

Following arterial occlusion, blood vessels respond by forming a new network of functional capillaries (angiogenesis), by re-organizing pre-existing capillaries through the recruitment of smooth muscle cells to generate new arteries (arteriogenesis) and by growing and remodeling pre-existing collateral arterioles into physiologically relevant arteries (collateral development). All these processes result in the recovery of organ perfusion. The importance of endoglin in post-occlusion reperfusion is sustained by several observations: i) endoglin expression is increased in vessels showing active angiogenesis/remodeling; ii) genetic endoglin haploinsufficiency in humans causes deficient angiogenesis; and iii) the reduction of endoglin expression by gene disruption or the administration of endoglin-neutralizing antibodies reduces angiogenesis and revascularization. However, the precise role of endoglin in the several processes associated with revascularization has not been completely elucidated and, in some cases, the function ascribed to endoglin by different authors is controversial. The purpose of this review is to organize in a critical way the information available for the role of endoglin in several phenomena (angiogenesis, arteriogenesis, and collateral development) associated with post-ischemic revascularization.

show abstract

“…In tumor vasculature, stromal-derived growth factor-1α (SDF1α) has been shown to promote PDGF-B-dependent pericyte migration via CXCR4 [86,87]. Interestingly, glioblastoma stem cell recruitment to the endothelium has been shown to be dependent in SDF1α/CXCR4, and their subsequent differentiation into pericytes has been induced by TGFβ [88].…”

Section: Other Pathwaysmentioning

confidence: 99%