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Haem relieves hyperoxia-mediated inhibition of HMEC-1 cell proliferation, migration and angiogenesis by inhibiting BACH1 expression.


ABSTRACT:

Background

Hyperoxia-mediated inhibition of vascular endothelial growth factor (VEGF) in the retina is the main cause of impeded angiogenesis during phase I retinopathy of prematurity (ROP). Human retinal angiogenesis involves the proliferation, migration and vessel-forming ability of microvascular endothelial cells. Previous studies have confirmed that BTB and CNC homology l (BACH1) can inhibit VEGF and angiogenesis, while haem can specifically degrade BACH1. However, the effect of haem on endothelial cells and ROP remains unknown.

Methods

In this report, we established a model of the relative hyperoxia of phase I ROP by subjecting human microvascular endothelial cells (HMEC-1) to 40% hyperoxia. Haem was added, and its effects on the growth and viability of HMEC-1 cells were evaluated. Cell counting kit 8 (CCK8) and 5-ethynyl-2'-deox-yuridine (EdU) assays were used to detect proliferation, whereas a wound healing assay and Matrigel cultures were used to detect the migration and vessel-forming ability, respectively. Western blot (WB) and immunofluorescence (IF) assays were used to detect the relative protein levels of BACH1 and VEGF.

Results

HMEC-1 cells could absorb extracellular haem under normoxic or hyperoxic conditions. The proliferation, migration and angiogenesis abilities of HMEC-1 cells were inhibited under hyperoxia. Moderate levels of haem can promote endothelial cell proliferation, while 20??M haem could inhibit BACH1 expression, promote VEGF expression, and relieve the inhibition of proliferation, migration and angiogenesis in HMEC-1 cells induced by hyperoxia.

Conclusions

Haem (20??M) can relieve hyperoxia-induced inhibition of VEGF activity in HMEC-1 cells by inhibiting BACH1 and may be a potential medicine for overcoming stunted retinal angiogenesis induced by relative hyperoxia in phase I ROP.

SUBMITTER: Jian L 

PROVIDER: S-EPMC7905865 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Haem relieves hyperoxia-mediated inhibition of HMEC-1 cell proliferation, migration and angiogenesis by inhibiting BACH1 expression.

Jian Lan L   Mei Yang Y   Xing Chen C   Rongdi Yuan Y  

BMC ophthalmology 20210225 1


<h4>Background</h4>Hyperoxia-mediated inhibition of vascular endothelial growth factor (VEGF) in the retina is the main cause of impeded angiogenesis during phase I retinopathy of prematurity (ROP). Human retinal angiogenesis involves the proliferation, migration and vessel-forming ability of microvascular endothelial cells. Previous studies have confirmed that BTB and CNC homology l (BACH1) can inhibit VEGF and angiogenesis, while haem can specifically degrade BACH1. However, the effect of haem  ...[more]

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2023-09-30 | GSE209958 | GEO