Bone marrow stromal cells attenuate oxygen and glucose deprivation followed by re‑oxygenation‑induced brain microvascular endothelial cell injury by mediating the plasminogen activator/plasminogen activator
receptor/stromal cell‑derived factor‑1α/C‑X‑C chemokine receptor type 4 pathway
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Published:2022-09-30
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ISSN:1689-0035
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Container-title:Acta Neurobiologiae Experimentalis
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language:
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Short-container-title:Acta Neurobiol Exp (Wars)
Author:
Fang Cui‑Ni,Song Tao,Tao Xi,Liu Shu‑Fen,Feng Zhen
Abstract
Ischemic stroke is a severe threat to the health of older individuals. Bone marrow mesenchymal stem cells (BMSCs) have been implicated in
ischemic stroke. Urokinase‑type plasminogen activator (uPA) and its specific receptor (uPAR) are associated with the pathological process
of ischemic stroke. However, the relationship between BMSCs and uPA/uPAR in ischemic stroke remains unclear. For simulating the
occurrence of an ischemic stroke in vitro, human cerebral microvascular endothelial cells (HBMECs) were subjected to oxygen and glucose
deprivation followed by re‑oxygenation (OGD/R) and were then cocultured with BMSCs. 3,4,5‑dimethylthiazol‑2,5‑diphenyltetrazolium
bromide and bromodeoxyuridine staining were used for measuring cell viability and proliferation. Flow cytometry was performed for
assessing cell apoptosis. Endothelial cell tube formation was determined using angiogenesis assays. Alterations in the protein and gene
expression in HBMECs were evaluated using western blot analysis and quantitative reverse transcription‑polymerase chain reaction,
respectively. OGD/R considerably inhibited the viability and proliferation of HBMECs by inducing apoptosis, which was reversed by
BMSCs. Consistently, OGD/R‑induced inhibition of angiogenesis was attenuated by BMSCs. In addition, BMSCs could protect HBMECs
against OGD/R‑induced injury by positively regulating the uPA/uPAR/stromal cell‑derived factor‑1α (SDF‑1α)/C‑X‑C chemokine receptor
type 4 (CXCR4) pathway, and uPA/uPAR could mediate the SDF‑1α/CXCR4 pathway in OGD/R‑treated HBMECs. Therefore, this study
provides novel strategies to investigate the specific role of BMSCs in ameliorating OGD/R‑induced vascular endothelial cell injury.
Publisher
The Nencki Institute of Experimental Biology, Polish Academy of Sciences
Subject
General Medicine,General Neuroscience