Search

Long non-coding (lnc)RNA hypoxia inducible factor 1α-antisense RNA 1 (HIF1A-AS1) not only participates in different types of malignancies, but also serves pivotal roles in thoracic aortic aneurysms, which suggests its possible involvement in intracranial aneurysms. Therefore, the present study aimed to investigate its involvement in intracranial aneurysms. Expression levels of HIF1A-AS1 and transforming growth factor (TGF)-β1 in the blood of patients with intracranial aneurysms and healthy controls were detected using reverse transcription-quantitative polymerase chain reaction. The diagnostic value of blood HIF1A-AS1 for intracranial aneurysms was analyzed using receiver operating characteristic curve analysis. A HIF1A-AS1 expression vector was constructed and transfected into human vascular smooth muscle cells (VSMCs) and the effects on cell proliferation and TGF-β1 expression were explored using the Cell Counting kit-8 assay and western blot analysis, respectively. Upregulated HIF1A-AS1 expression levels in blood were observed in patients with intracranial aneurysms when compared with controls. Notably, upregulated HIF1A-AS1 expression effectively distinguished patients with intracranial aneurysms from healthy controls. Furthermore, HIF1A-AS1 and TGF-β1 expression levels were positively correlated with intracranial aneurysms. HIF1A-AS1 overexpression also upregulated TGF-β1 expression and inhibited VSMC proliferation. Although TGF-β1 treatment had no significant effect on HIF1A-AS1 expression, TGF-β inhibitor significantly reduced the effects of HIF1A-AS1 overexpression on cell proliferation. It was therefore concluded that HIF1A-AS1 may participate in intracranial aneurysms by regulating VSMC proliferation through the upregulation of TGF-β1. [ABSTRACT FROM AUTHOR]

Neural tube defects (NTDs) are the most serious and common birth defects in the clinical setting. The Notch signaling pathway has been implicated in different processes of the embryonic neural stem cells (NSCs) during neural tube development. The aim of the present study was to investigate the expression pattern and function of Notch1 (N1) in all-trans retinoic acid (atRA)-induced NTDs and NSC differentiation. A mouse model of brain abnormality was established by administering 28 mg/kg atRA, and then brain development was examined using hematoxylin and eosin (H&E) staining. The N1 expression pattern was detected in the brain of mice embryos via immunohistochemistry and western blotting. NSCs were extracted from the fetal brain of C57 BL/6 embryos at 18.5 days of pregnancy. N1, Nestin, neurofilament (NF), glial fibrillary acidic protein (GFAP) and galactocerebroside (GALC) were identified using immunohistochemistry. Moreover, N1, presenilin 1 (PS1), Nestin, NF, GFAP and GALC were detected via western blotting at different time points in the NSCs with control media or atRA media. H&E staining identified that the embryonic brain treated with atRA was more developed compared with the control group. N1 was downregulated in the embryonic mouse brain between days 11 and 17 in the atRA-treated group compared with the untreated group. The distribution of N1, Nestin, NF, GFAP and GALC was positively detected using immunofluorescence staining. Western blotting results demonstrated that there were significantly, synchronous decreased expression levels of N1 and PS1, but increased expression levels of NF, GFAP and GALC in NSCs treated with atRA compared with those observed in the controls (P<0.05). The results suggested that the N1 signaling pathway inhibited brain development and NSC differentiation. Collectively, it was found that atRA promoted mouse embryo brain development and the differentiation of NSCs by inhibiting the N1 pathway. [ABSTRACT FROM AUTHOR]