Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury

Du, Mengjie; Wang, Na; Xin, Xiaolong; Yan, Chunxiao; Yan, Gu; Wang, Liang; Shen, Ying

doi:10.3389/fcell.2023.1163400

Cited by 5 publications

(1 citation statement)

References 65 publications

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“…It plays a role in regulating neuronal excitability and synaptic plasticity in the hippocampus [43]. Edn1 is involved in regulating neurotransmission, microglial proliferation, and maintenance, and EDN1-endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury [43][44][45]. Ier3 gene is involved in regulating apoptosis in various organs [46,47], and its role in preterm brain injury is unknown.…”

Section: Pathways In the Hippocampusmentioning

confidence: 99%

GSDMD gene knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice

Challa,

Chen,

Yun

et al. 2023

Preprint

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Background: Neonatal hyperoxia exposure is associated with brain injury and poor neurodevelopment outcomes in preterm infants. Our previous studies in neonatal rodent models have shown that hyperoxia stimulates the brain’s inflammasome pathway, leading to the activation of gasdermin D (GSDMD), a key executor of pyroptotic inflammatory cell death. Moreover, we found inhibition of GSDMD activation attenuates hyperoxia-induced brain injury in neonatal mice. We hypothesized that GSDMD plays a pathogenic role in hyperoxia-induced neonatal brain injury and that GSDMD gene knockout (KO) will alleviate hyperoxia-induced brain injury. Methods: Newborn GSDMD knockout mice and their wildtype (WT) littermates were randomized within 24 h after birth to be exposed to room air or hyperoxia (85% O2) from postnatal day 1 to 14. Hippocampal brain inflammatory injury was assessed in brain sections by immunohistology for allograft inflammatory factor 1 (AIF1), a marker of microglial activation. Cell proliferation was evaluated by Ki-67 staining, and cell death was determined by TUNEL assay. RNA sequencing of the hippocampus was performed to identify the transcriptional effects of hyperoxia and GSDMD-KO, and qRT-PCR was performed to confirm some of the significantly regulated genes. Results: Hyperoxia-exposed WT mice had increased microglia consistent with activation, which was associated with decreased cell proliferation and increased cell death in the hippocampal area. Conversely, hyperoxia-exposed GSDMD-KO mice exhibited considerable resistance to hyperoxia as O2 exposure failed to increase either AIF1+ or TUNEL+ cell numbers, nor decrease cell proliferation. Hyperoxia exposure differentially regulated 258 genes in WT and only 16 in GSDMD-KO mice compared to room air- exposed WT and GSDMD-KO, respectively. Gene set enrichment analysis showed that in the WT brain, hyperoxia differentially regulated genes associated with neuronal and vascular development and differentiation, axonogenesis, glial cell differentiation, and core development pathways hypoxia-induced factor 1, and neuronal growth factor pathways. These changes were prevented by GSDMD-KO. Conclusion: GSDMD-KO alleviates hyperoxia-induced inflammatory injury, cell survival and death, and alterations of transcriptional gene expression of pathways involved in neuronal growth, development, and differentiation in the hippocampus of neonatal mice. This suggests that GSDMD plays a pathogenic role in preterm brain injury, and targeting GSDMD may be beneficial in preventing and treating brain injury and poor neurodevelopmental outcomes in preterm infants.

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Section: Pathways In the Hippocampusmentioning

confidence: 99%

GSDMD gene knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice

Challa,

Chen,

Yun

et al. 2023

Preprint

View full text Add to dashboard Cite

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Korean Red Ginseng and Rb1 restore altered social interaction, gene expressions in the medial prefrontal cortex, and gut metabolites under post-weaning social isolation in mice

Kwon,

Hwang Park,

Kim

et al. 2024

Journal of Ginseng Research

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Endothelin-1 impairs skeletal muscle myogenesis and development via ETB receptors and p38 MAPK signaling pathway

Liu,

Chen,

Jhong

et al. 2024

Clinical Science

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Myopenia is a condition marked by progressive decline of muscle mass and strength and is associated with aging or obesity. It poses the risk of falling, with potential bone fractures, thereby also increasing the burden on family and society. Skeletal muscle wasting is characterized by a reduced number of myoblasts, impaired muscle regeneration and increased muscle atrophy markers (Atrogin-1, MuRF-1). Endotheline-1 (ET-1) is a potent vasoconstrictor peptide. Increased circulating levels of ET-1 is noted with aging and is associated with muscular fibrosis and decline of strength. However, the regulatory mechanism controlling its effect on myogenesis and atrophy remains unknown. In the present study, the effects of ET-1 on myoblast proliferation, differentiation and development were investigated in C2C12 cells and in ET-1-infused mice. The results show that ET-1, acting via ETB receptors, reduced insulin-stimulated cell proliferation, and also reduced MyoD, MyoG and MyHC expression in the differentiation processes of C2C12 myoblasts. ET-1 inhibited myoblast differentiation through ETB receptors and the p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Additionally, ET-1 decreased MyHC expression in differentiated myotubes. Inhibition of proteasome activity by MG132 ameliorated the ET-1-stimulated protein degradation in differentiated C2C12 myotubes. Furthermore, chronic ET-1 infusion caused skeletal muscle atrophy and impaired exercise performance in mice. In conclusion, ET-1 inhibits insulin-induced cell proliferation, impairs myogenesis and induces muscle atrophy via ETB receptors and the p38 MAPK-dependent pathway.

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Endothelin-1–Endothelin receptor B complex contributes to oligodendrocyte differentiation and myelin deficits during preterm white matter injury

Cited by 5 publications

References 65 publications

GSDMD gene knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice

GSDMD gene knockout alleviates hyperoxia-induced hippocampal brain injury in neonatal mice

Korean Red Ginseng and Rb1 restore altered social interaction, gene expressions in the medial prefrontal cortex, and gut metabolites under post-weaning social isolation in mice

Endothelin-1 impairs skeletal muscle myogenesis and development via ETB receptors and p38 MAPK signaling pathway

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