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An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma [Day 4]

ABSTRACT: An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma [Day 4]

PROVIDER: PRJNA1148977 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30274412_1.fastq.gz	Fastqsanger.gz
	SRR30274412_2.fastq.gz	Fastqsanger.gz
	SRR30274413_1.fastq.gz	Fastqsanger.gz
	SRR30274413_2.fastq.gz	Fastqsanger.gz
	SRR30274414_1.fastq.gz	Fastqsanger.gz

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An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma [Day 4]

Project description:Infantile hemangioma (IH) is the most common tumor in children and a paradigm for pathological vasculogenesis, angiogenesis and regression. Propranolol is the mainstay of treatment for IH. It inhibits hemangioma vessel formation via a β-adrenergic receptor independent effect of its R(+) enantiomer on the endothelial specific transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18). Transcriptomic profiling of patient-derived hemangioma stem cells uncovered the mevalonate pathway (MVP) as a target of R(+) propranolol. Loss of SOX18 function confirmed R(+) propranolol mode of action on the MVP. Functional validation in preclinical IH models revealed that statins - targeting the MVP - are potent inhibitors of hemangioma vessel formation. We propose a novel SOX18-MVP-axis as a central regulator of IH pathogenesis and suggest statin repurposing to treat IH.

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An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma [Day 6]

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An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma [Day 6]

Project description:An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma [Day 6]

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microRNA analysis of infantile hemangioma, lymphatic malformation, and skin

Project description:Surgical specimens from children with infantile hemangioma or lymphatic malformations, as well as healthy appearing adjacent skin, were analyzed by microarray analysis of microRNA expression. Unsupervised hierarchical clustering was performed to identify microRNAs that were differentially expressed in IH compared to lymphatic malformations and skin 19 patients who underwent surgical excision of either a lymphatic malformation or infantile hemangioma were used in the study. 5 patients have multiple samples on the array and these duplicates are from different regions of the excised tissue or separate lesions as indicated. Tissue was snap frozen in liquid nitrogen and used for RNA extraction

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OTUB1 catalytic-independently deubiquitinates TGFBI and mediates the angiogenesis in infantile hemangioma by regulating glycolysis

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Genome-wide transcriptome comparison between primary cultures of human dermal microvascular endothelial cells and infantile hemangioma endothelial cells

Project description:Whole transcriptome comparisons of proliferating pure cultures of neonatal dermal microvacsular endothelial cells to infantile hemangioma endothelial cells. The total RNA was obtained from human dermal microvascular endothelial cells and infantile hemangioma endothelial cells. Illumina microarrays were performed to determine the whole genome expression differences between the cell lines.

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Project description:Infantile hemangioma (IH) was one of the most common vascular tumors during childhood. Long non coding RNAs (lncRNAs) play great roles in angiogenesis; the involvement of lncRNAs in hemangioma remains unknown. We aim to investigate the differential expression of lncRNA between hemangioma and the adjacent normal tissues, with a view to studying the biological function of lncRNAs and their involvement in the pathogenesis of hemangioma. The differential lncRNAs expression profiles of hemangioma were established by lncRNA microarray. Bioinformatic analyses were applied for further study of these differentially expressed lncRNAs. A total of 2116 differentially expressed lncRNAs were identified, among these lncRNAs, 1259 were up-regulated and 857 were down-regulated more than two-fold.

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CD146+ mural cells from infantile hemangioma

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Project description:In order to understand the mechanisms underlying the effects of itraconazole in infantile hemangioma endothelial cells, we further explored the potential targeting genes of itraconazole in infantile hemangioma endothelial cells in vitro by using a genome-wide gene expression array. In total 172 mRNAs were up-regulated (fold change > 2) and 819 mRNAs were down-regulated (fold change > 2) upon itraconazole treatment in infantile hemangioma endothelial cells. The top signaling pathway closely related to differentially expressed genes upon itraconazole treatment is the cytokine and cytokine receptor pathway. Within this pathway, the mRNA expression of PDGF-D, an important growth factor belonging to the PDGF family, was the most significantly reduced (30 folds) among 991 differentially expressed genes after itraconazole treatment. qRT-PCR and western blotting confirmed the inhibitory effects on PDGF-D levels.

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