MiR-124 affects the apoptosis of brain vascular endothelial cells and ROS production through regulating PI3K/AKT signaling pathway
Authors: S-L Ye
W-Y Xu
S-W Wang
L-X Deng
Z-Q Su
H-Y Chen
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: apoptosis; vascular endothelial cells; miR-124; PI3K; AKT
Affiliations: Department of Neurology, the Third Hospital of Xiamen, Xiamen, Fujian, China. .

Abstract:  Objective: The apoptosis of vascular endothelial cells (VEC) is related to ischemic stroke. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway can upregulate Bcl-2 expression, reduce reactive oxygen species (ROS) production, and induce apoptosis. The level of miR-124 was significantly increased after cerebral ischemia. This study aimed to investigate the role of miR-124 in regulating PI3K expression, brain VEC apoptosis, and ROS production. Materials and methods: The expressions of miR-124, PI3K, p-AKT, and Bcl-2 in brain VEC of rats from the sham group and middle cerebral artery occlusion (MCAO) group were tested. Bioinformatics analysis showed the complementary binding site between miR-124 and PI3K mRNA. ROS content and cell apoptosis were detected by flow cytometry. Rat brain VEC were cultured in vitro and treated by oxygen-glucose deprivation (OGD) for 6 h. VECs were divided into four groups, including miR-NC, miR-124 inhibitor, pIRES2-blank, and pIRES2-PI3K groups, and were further treated by OGD. Results: MiR-124 expression, ROS content, and cell apoptosis were markedly increased, whereas the levels of PI3K, p-AKT, and Bcl-2 were markedly reduced in rat VECs from MCAO group compared with that in the sham group. OGD treatment significantly induced VECs apoptosis, upregulated miR-124 expression and ROS content, and down-regulated the levels of PI3K, p-AKT, and Bcl-2. MiR-124 inhibitor or transfection of pIRES2-PI3K plasmid apparently enhanced PI3K, p-AKT, and Bcl-2 expressions, alleviated cell apoptosis and decreased ROS content in VECs induced by OGD. Conclusions: Our data demonstrated that miR-124 induced the apoptosis of brain vascular endothelial cells via the down-regulation of PI3K/AKT signaling pathway and promotion of ROS production. 

Retracted: Yes

PubPeer comments:
 At right:  Figure 5. Downregulation of miR-124 or enhancement of PI3K attenuated VECs apoptosis induced by OGD. ... (C) Flow cytometry detection on cell apoptosis . From [Wang et al (2018)] . ![file] Above left,  Figure 3. Inhibition of miR-221 up-regulated SOCS3 expression, suppressed T24 cell proliferation, and promoted apoptosis. ... (C) flow cytometry detection of cell apoptosis;  From [Liu et al (2017)] . Below left,  Figure 4. Over-expression of miR-107 suppressed DDP resistance and facilitated cell apoptosis of U251 DDP cells. ... (D) EdU staining for cell proliferation potency; (E) Flow cytometry for cell apoptosis . From [Su Song (2018)] . Despite some customising, the panels are more similar than dissimilar. This is despite the completely different miRs and cell lines, and the lack of overlap between authors. , 
 Also of note: Refs 1 to 14, and 20-24, deal with Rinderpest and Canine Distemper and other morbilliviruses, with no obvious relevance to miR or brain vasculature. 1) Forsyth MA, Barrett T. Evaluation of polymerase chain reaction for the detection and characterisation of rinderpest and peste des petits ruminants viruses for epidemiological studies. Virus Res 1995; 39: 151-163. 2) Ismai l TM, Yama naka MK, Saliki JT, el-Kholy A, Mebus C, Yilma T. Cloning and expression of the nucleoprotein of peste des petits ruminants virus in baculovirus for use in serological diagnosis. Virology 1995; 208: 776-778. 3) Lib eau G, Prehaud C, Lancelot R, Colas F, Guerre L, Bishop DH , Dia llo A. Development of a competitive ELISA for detecting antibodies to the peste des petits ruminants virus using a recombinant nucleoprotein. Res Vet Sci 1995; 58: 50-55. 4) Meyer G, Dia llo A. The nucleotide sequence of the fusion protein gene of the peste des petits ruminants virus: the long untranslated region in the 5u2019-end of the F-protein gene of morbilliviruses seems to be specific to each virus. Virus Res 1995; 37: 23-35. 5) Romero CH, Barrett T, Kitching RP, Bostock C, Blac k DN . Protection of goats against peste des petits ruminants with recombinant capripoxviruses expressing the fusion and haemagglutinin protein genes of rinderpest virus. Vaccine 1995; 13: 36-40. , 
 #1 Extended into a Gallery of Unfortunate FACS Plots. Please excuse the length. This is a random assortment from a certain oeuvre. Any other of ~40 papers from the same journal(s) could have been used instead. I have only marked a few of the recurring constellations of points. Colored plots darkened and contrast-enhanced for visibility. Fig 4C [Liu et al (2017)] PMID 28770966 Fig 2D, 3D [Wu et al (2017)] PMID 28617558 Fig 2D [Liang et al (2017)] PMID 29164556 ![file] Fig 3E [Li et al (2018)] 10.26355 eurrev_201809_15933 Fig 4D [Dong et al (2018)] 10.26355 eurrev_201805_15059 Fig 4D [Song et al (2018)] 10.26355 eurrev_201806_15153 ![file] Fig 2B, 4B, 5C [Wang et al (2018)] 10.26355 eurrev_201801_14201 Fig 3B, 4E [Su Song (2018)] 10.26355 eurrev_201810_16155 Fig 2D [Han et al (2018)] 10.26355 eurrev_201811_16390 ![file] Fig 4C [Wang Yu (2019)] 10.26355 eurrev_201903_17397 Fig 5D [Zhou et al (2019)] 10.26355 eurrev_201911_19436 Fig 4E [Liu Zhang (2019)] 10.1089 cbr.2018.2749 Fig 4D [Piao et al (2019)] 10.1089 cbr.2018.2625 ![file] , 
 It may also be worth documenting the curious stylized renditions of Western Blots favoured by this production studio (and by the editors and reviewers who accept this oeuvre of papers). ![file] , 
 Retracted [July 2021] . ---------------------------- The article u201cMiR-124 affects the apoptosis of brain vascular endothelial cells and ROS production through regulating PI3K AKT signaling pathway, by S.-W. Wang, L.-X. Deng, H.-Y. Chen, Z.-Q. Su, S.-L. Ye, W.-Y. Xu, published in Eur Rev Med Pharmacol Sci 2018; 22 (2): 498-505u2013DOI: 10.26355 eurrev_201801_14201u2013PMID: 29424909u201d has been withdrawn from the authors due to inaccuracies (there are some errors and incorrect data). The Publisher apologizes for any inconvenience this may cause. ,