The alternative 3' splice site of GPNMB may promote neuronal survival after neonatal hypoxic-ischemic encephalopathy injury.
Guo-Jiao ChenShan-Shan YanJing-Han ZhangJi ZhangIsaac Bul DengRong HePublished in: Ibrain (2022)
This study aimed to decipher the effect of glycoprotein nonmetastatic melanoma protein B ( GPNMB ) on neonatal hypoxic-ischemic encephalopathy (NHIE) and its potential molecular mechanism. The hypoxic-ischemic (HI) model was established in 7-day-old rats, and then, Zea-Longa scores and Nissl staining were performed to measure brain damage post-HI. In addition, gene sequencing was used to detect the differential expression genes (DEGs), and then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to determine the function of DEGs. Furthermore, an oxygen-glucose deprivation (OGD) model was developed in SY5Y cells and human fetal neurons, and then, the level of GPNMB was verified by quantitative real-time polymerase chain reaction. In addition, methyl thiazolyl tetrazolium and cell counting kit-8 assays were applied after GPNMB interference. Finally, the alternative splicing of GPNMB expression was analyzed using Splice Grapher software. The results indicated that HI induced marked neurological impairment and neuron injury in rats. Also, GPNMB was the most obviously upregulated gene in DEGs. Additionally, GPNMB was upregulated significantly in SY5Y and fetal neurons after OGD, and GPNMB-si promoted an increase in cell viability and number. Moreover, we found that the GPNMB alternative splicing type was the Alternative 3' splice site, with the alternative splicing site in 143382985:143404102. Herein, GPNMB promotes a crucial regulatory mechanism with alternative splicing for neuronal survival after NHIE.
Keyphrases
- genome wide
- genome wide identification
- endothelial cells
- single cell
- oxidative stress
- spinal cord
- early onset
- machine learning
- transcription factor
- induced apoptosis
- gene expression
- metabolic syndrome
- mass spectrometry
- cell death
- signaling pathway
- white matter
- room temperature
- bone marrow
- adipose tissue
- artificial intelligence
- long non coding rna
- high glucose
- big data