RGD Reference Report - Knockdown of HIF-1α impairs post-ischemic vascular reconstruction in the brain via deficient homing and sprouting bmEPCs. - Rat Genome Database

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Knockdown of HIF-1α impairs post-ischemic vascular reconstruction in the brain via deficient homing and sprouting bmEPCs.

Authors: Liu, Yang  Ran, He  Xiao, Yaping  Wang, Hongjin  Chen, Yi  Chen, Weihai  Xu, Xiaoyu 
Citation: Liu Y, etal., Brain Pathol. 2018 Nov;28(6):860-874. doi: 10.1111/bpa.12628. Epub 2018 Oct 9.
RGD ID: 155663378
Pubmed: PMID:30052311   (View Abstract at PubMed)
PMCID: PMC8028501   (View Article at PubMed Central)
DOI: DOI:10.1111/bpa.12628   (Journal Full-text)

Although the critical role of hypoxia inducible factor-1α (HIF-1α) in cerebral neovascularization after stroke has been well characterized, the details regarding the regulation of endothelial progenitor cell (EPC)-dependent neovascularization by HIF-1α are not completely understood. Using lentiviral shRNA to knockdown HIF-1α, we showed that HIF-1α plays a central role in bone marrow-derived EPC (bmEPC) homing and sprouting in the post-acute stage of ischemic Sprague Dawley (SD) rat brains. First, knockdown of HIF-1α decreased the homing of both endogenous and exogenous bmEPCs to the ischemic brain. Additionally, the knockdown impaired the incorporation and sprouting of bmEPCs in the ischemic brain. In vitro, knockdown of HIF-1α inhibited the spheroid sprouting and tube formation of bmEPCs. Mechanically, the HIF-1α-dependent recruitment of bmEPCs to the ischemic brain was relative to the CXCL12/CXCR4 axis and HMGB1, which were relative to astrocytes. In addition, the loss of HIF-1α resulted in deficient expression levels of VEGF-A, Flk-1, NRP1, and Dll4 in the ischemic brains, bmEPCs, and astrocytes. These findings suggested that HIF-1α implicates in bmEPC homing via CXCL12/CXCR4 and HMGB1 and that it promotes bmEPC sprouting via VEGF-A/flk1-NRP1/Dll4.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
brain infarction exacerbatesISOHif1a (Rattus norvegicus)155663378; 155663378 RGD 
brain infarction exacerbatesIMP 155663378 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Hif1a  (hypoxia inducible factor 1 subunit alpha)

Genes (Mus musculus)
Hif1a  (hypoxia inducible factor 1, alpha subunit)

Genes (Homo sapiens)
HIF1A  (hypoxia inducible factor 1 subunit alpha)


Additional Information