NOTCH3 regulates stem-to–mural cell differentiation in infantile hemangioma

Edwards, Andrew K.; Glithero, Kyle J; Grzesik, Peter; Kitajewski, Alison A.; Munabi, Naikhoba C.O.; Hardy, Krista L.; Tan, Qian; Schonning, Michael J; Kangsamaksin, Thaned; Kitajewski, Jan; Shawber, Carrie J.; Wu, June K.

doi:10.1172/jci.insight.93764

Cited by 22 publications

(21 citation statements)

References 57 publications

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“…Nevertheless, increased expression of stem cell transcription factors OCT4, SOX2, NANOG and MYC have been reported in IH 6 . In addition, our in vivo data also show that in proliferative IH LIN28 was not limited to GLUT1 positive cells but was also expressed in perivascular non-endothelial cells, which are essential for the maintenance of IH vessels stability 47 .…”

Section: Discussionsupporting

confidence: 62%

Modulation of LIN28B/Let-7 Signaling by Propranolol Contributes to Infantile Hemangioma Involution

Mong¹,

Akat

Canfield³

et al. 2018

ATVB

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Section: Discussionsupporting

confidence: 62%

Modulation of LIN28B/Let-7 Signaling by Propranolol Contributes to Infantile Hemangioma Involution

Mong¹,

Akat

Canfield³

et al. 2018

ATVB

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“…Serial sections (5μm) were deparaffinized, rehydrated, and blocked as previously described [ 24 ]. Primary antibodies ( S1 Table ) were detected with Alexa Fluor-conjugated Donkey-secondary antibodies at 1:1000 (Invitrogen) and slides mounted with DAPI Mounting Media (Vector).…”

Section: Methodsmentioning

confidence: 99%

Venous malformation vessels are improperly specified and hyperproliferative

et al. 2021

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Venous malformations (VMs) are slow-flow malformations of the venous vasculature and are the most common type of vascular malformation with a prevalence of 1%. Germline and somatic mutations have been shown to contribute to VM pathogenesis, but how these mutations affect VM pathobiology is not well understood. The goal of this study was to characterize VM endothelial and mural cell expression by performing a comprehensive expression analysis of VM vasculature. VM specimens (n = 16) were stained for pan-endothelial, arterial, venous, and endothelial progenitor cell proteins; proliferation was assessed with KI67. Endothelial cells in the VM vessels were abnormally orientated and improperly specified, as seen by the misexpression of both arterial and endothelial cell progenitor proteins not observed in control vessels. Consistent with arterialization of the endothelial cells, VM vessels were often surrounded by multiple layers of disorganized mural cells. VM endothelium also had a significant increase in proliferative endothelial cells, which may contribute to the dilated channels seen in VMs. Together the expression analysis indicates that the VM endothelium is misspecified and hyperproliferative, suggesting that VMs are biologically active lesions, consistent with clinical observations of VM progression over time.

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“…These results suggest that NGBR also was required for RTK growth factor–induced migration of HemSCs. Mesenchymal features have been identified in infantile hemangioma ( 38 – 40 ). However, NGBR knockdown did not change the expression of mesenchymal markers (vimentin and N-cadherin) and epithelial marker (E-cadherin) ( Supplemental Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

NOGOB receptor–mediated RAS signaling pathway is a target for suppressing proliferating hemangioma

Liu

Salato

et al. 2021

JCI Insight

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Infantile hemangioma is a vascular tumor characterized by the rapid growth of disorganized blood vessels followed by slow spontaneous involution. The underlying molecular mechanisms that regulate hemangioma proliferation and involution still are not well elucidated. Our previous studies reported that NOGOB receptor (NGBR), a transmembrane protein, is required for the translocation of prenylated RAS from the cytosol to the plasma membrane and promotes RAS activation. Here, we show that NGBR was highly expressed in the proliferating phase of infantile hemangioma, but its expression decreased in the involuting phase, suggesting that NGBR may have been involved in regulating the growth of proliferating hemangioma. Moreover, we demonstrate that NGBR knockdown in hemangioma stem cells (HemSCs) attenuated growth factor–stimulated RAS activation and diminished the migration and proliferation of HemSCs, which is consistent with the effects of RAS knockdown in HemSCs. In vivo differentiation assay further shows that NGBR knockdown inhibited blood vessel formation and adipocyte differentiation of HemSCs in immunodeficient mice. Our data suggest that NGBR served as a RAS modulator in controlling the growth and differentiation of HemSCs.

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NOTCH3 regulates stem-to–mural cell differentiation in infantile hemangioma

Cited by 22 publications

References 57 publications

Modulation of LIN28B/Let-7 Signaling by Propranolol Contributes to Infantile Hemangioma Involution

Modulation of LIN28B/Let-7 Signaling by Propranolol Contributes to Infantile Hemangioma Involution

Venous malformation vessels are improperly specified and hyperproliferative

NOGOB receptor–mediated RAS signaling pathway is a target for suppressing proliferating hemangioma

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