Experimental Study on the Correlation between miRNA-373 and HIF-1α, MMP-9, and VEGF in the Development of HIE

Liu, Chunyang; Al-Ward, Hisham; Mekontso, Francine Ngaffo; Liu, Ning; Zeng, Huiqin; Liu, Min; Yu, Zirui; Zhang, Lin; Han, Yuchun; Xu, Hui

doi:10.1155/2021/5553486

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…Studies in infants with HIE have shown that levels of miR-374a, miR-376c, miR-161b, and miR-181b are decreased in umbilical cord blood (which contains the highest level and activity of RNase1 compared to other blood sources) and could distinguish infants affected by perinatal asphyxia or HIE from healthy infants (Looney et al, 2015(Looney et al, , 2019O'Sullivan et al, 2019). Meanwhile, miR-373 was found to be increased and positively correlates with levels of VEGF, MMP-9, and HIF-1α in infants with HIE (Liu et al, 2021), while miR-210 exhibits increased levels in a piglet model of global hypoxia (Garberg et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Treatment with RNase alleviates brain injury but not neuroinflammation in neonatal hypoxia/ischemia

Anderberg,

Andersson,

Bucher

et al. 2024

J of Neuroscience Research

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There is a need for new treatments to reduce brain injuries derived from neonatal hypoxia/ischemia. The only viable option used in the clinic today in infants born at term is therapeutic hypothermia, which has a limited efficacy. Treatments with exogenous RNase have shown great promise in a range of different adult animal models including stroke, ischemia/reperfusion injury, or experimental heart transplantation, often by conferring vascular protective and anti‐inflammatory effects. However, any neuroprotective function of RNase treatment in the neonate remains unknown. Using a well‐established model of neonatal hypoxic/ischemic brain injury, we evaluated the influence of RNase treatment on RNase activity, gray and white matter tissue loss, blood–brain barrier function, as well as levels and expression of inflammatory cytokines in the brain up to 6 h after the injury using multiplex immunoassay and RT‐PCR. Intraperitoneal treatment with RNase increased RNase activity in both plasma and cerebropinal fluids. The RNase treatment resulted in a reduction of brain tissue loss but did not affect the blood–brain barrier function and had only a minor modulatory effect on the inflammatory response. It is concluded that RNase treatment may be promising as a neuroprotective regimen, whereas the mechanistic effects of this treatment appear to be different in the neonate compared to the adult and need further investigation.

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Section: Discussionmentioning

confidence: 99%

Treatment with RNase alleviates brain injury but not neuroinflammation in neonatal hypoxia/ischemia

Anderberg,

Andersson,

Bucher

et al. 2024

J of Neuroscience Research

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“…Limd1, a LIM domain-containing protein, has been extensively studied in various cancers, where it has shown negative effects on tumor growth (Foxler et al 2018 ; Zhou et al 2019a , b ; Huggins et al 2017 ; Huggins and Andrulis 2008 ; Sharp et al 2008 ; Liu et al 2021 ). However, its involvement in HIBD has been largely unexplored.…”

Section: Discussionmentioning

confidence: 99%

LncRNA-mir3471-limd1 regulatory network plays critical roles in HIBD

Sun,

Wan,

Sun

et al. 2023

Exp Brain Res

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The purpose of this study was to identify the target genes of tcon_00044595, elucidate its activation site, and provide novel insights into the pathogenesis and treatment of neonatal hypoxic–ischemic brain damage (HIBD). Through homologous blast analysis, we identified predicted target sequences in the neighboring regions of the long non-coding RNA (lncRNA) tcon_00044595, suggesting that limd1 is its target gene. Starbase was utilized to identify potential candidate microRNAs associated with the lncRNA. The interaction between the candidate microRNAs and limd1 was investigated and validated using various experimental methods including in vitro cell culture, cell transfection, dual fluorescence reporter detection system, and real-time PCR. Homology alignment analysis revealed that the lncRNA tcon_00044595 exhibited a 246 bp homologous sequence at the 3' end of the adjacent limd1 gene, with a conservation rate of 68%. Analysis conducted on Starbase online identified three potential microRNA candidates: miR-3471, miR-883a-5p, and miR-214-3p. Intracellular expression of the limd1 gene was significantly down-regulated upon transfection with miR-3471, while the other two microRNAs did not produce noticeable effects. Luciferase reporter assays identified two interaction sites (UTR-1, UTR-2) between miR-3471 and the limd1 3ʹUTR, with UTR-1 exhibiting a strong influence. Further CCK8 assay indicated a protective role of miR-3471 during low oxygen stroke in HIBD. The potential regulatory relationship between lncRNA (tcon_00044595), miR-3471, and the target gene limd1 suggests their involvement in the occurrence and development of HIBD, providing new insights for investigating the underlying mechanisms and exploring targeted therapeutic approaches for HIBD.

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“…This neurotrophin, secreted by central nervous system neurons and astrocytes, is involved in neuronal survival and synaptic plasticity [ 46 , 47 ]. Liu et al [ 68 ] also showed an increase in serum matrix metalloproteinase-9 (MMP-9) in neonates with HIE. MMP-9 is involved in the disruption of the blood–brain barrier by degrading brain vasculature basement membrane components [ 47 ].…”

Section: Proteomicsmentioning

confidence: 99%

Diagnostic and Therapeutic Roles of the “Omics” in Hypoxic–Ischemic Encephalopathy in Neonates

Rasineni¹,

Panigrahy

Rath

et al. 2022

Bioengineering

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Perinatal asphyxia and neonatal encephalopathy remain major causes of neonatal mortality, despite the improved availability of diagnostic and therapeutic tools, contributing to neurological and intellectual disabilities worldwide. An approach using a combination of clinical data, neuroimaging, and biochemical parameters is the current strategy towards the improved diagnosis and prognosis of the outcome in neonatal hypoxic–ischemic encephalopathy (HIE) using bioengineering methods. Traditional biomarkers are of little use in this multifactorial and variable phenotype-presenting clinical condition. Novel systems of biology-based “omics” approaches (genomics, transcriptome proteomics, and metabolomics) may help to identify biomarkers associated with brain and other tissue injuries, predicting the disease severity in HIE. Biomarker studies using omics technologies will likely be a key feature of future neuroprotective treatment methods and will help to assess the successful treatment and long-term efficacy of the intervention. This article reviews the roles of different omics as biomarkers of HIE and outlines the existing knowledge of our current understanding of the clinical use of different omics molecules as novel neonatal brain injury biomarkers, which may lead to improved interventions related to the diagnostic and therapeutic aspects of HIE.

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Experimental Study on the Correlation between miRNA-373 and HIF-1α, MMP-9, and VEGF in the Development of HIE

Cited by 5 publications

References 29 publications

Treatment with RNase alleviates brain injury but not neuroinflammation in neonatal hypoxia/ischemia

Treatment with RNase alleviates brain injury but not neuroinflammation in neonatal hypoxia/ischemia

LncRNA-mir3471-limd1 regulatory network plays critical roles in HIBD

Diagnostic and Therapeutic Roles of the “Omics” in Hypoxic–Ischemic Encephalopathy in Neonates

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