scholarly journals YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2

2021 ◽  
Author(s):  
Xiaotang Wang ◽  
Wei Fan ◽  
Na Li ◽  
Guoqing Wang ◽  
Siyuan He ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Transcription Activation ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Ocular Neovascularization ◽  
Yin Yang 1 ◽  
Retinal Microglia ◽  
Fgf2 Expression ◽  
Underlying Mechanisms

Abstract Ocular neovascularization is a leading cause of blindness. Retinal microglia have been implicated in hypoxia-induced angiogenesis and vasculopathy, but the underlying mechanisms remain largely unknown. Here, we report that lactylation in microglia is critical for retinal neovascularization. Using lactylome and proteomic analyses, we identified a list of hyperlactylated proteins in the context of increased lactate under hypoxia. Yin Yang-1 (YY1), a transcription factor, is lactylated at lysine 183 (K183) under hypoxia, which is regulated by p300. Furthermore, hyperlactylated YY1 directly enhances fibroblast growth factor 2 (FGF2) transcription and promotes angiogenesis. YY1 mutation at K183 eliminates these effects. Notably, clinical retrospective analysis shows that lactate concentrations in retinopathy of prematurity (ROP) infants are significantly increased compared with those in controls. Taken together, our results demonstrate that YY1 lactylation in microglia promotes FGF2 expression and plays a pivotal proangiogenic role, providing new insights into retinal neovascular diseases.

scholarly journals Fibroblast growth factor-2 prevents synaptic pathology in minimal hepatic encephalopathy via NRG1/ErbB4 signaling

2019 ◽  
Author(s):  
Jian Wang ◽  
Weishan Zhuge ◽  
Xiaoai Lu ◽  
Ruimin You ◽  
Leping Liu ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Memory Function ◽  
Minimal Hepatic Encephalopathy ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Neuregulin 1 ◽  
Synaptic Pathology ◽  
Fgf2 Expression

AbstractBackgroundMinimal hepatic encephalopathy (MHE) is implicated in the impairment of memory function. Fibroblast growth factor-2 (FGF2) is involved in modulating synaptic and neuronal formation.MethodsThe aim of this study is to examined the impacts of FGF2 on MHE pathology. Our study addressed whether FGF2 could trigger neuregulin-1 (NRG1) release to ameliorate synaptic impairment in MHE rats and in primary cultured neurons.ResultsThe results showed the decreased FGF2 expression in MHE brains. After treatment with FGF2, secreted neuregulin-1 (NRG1) and ErbB4 were increased, and the interaction of the 2 proteins was enhanced. Additionally, treatment with FGF2 or NRG1 induced synaptic formation, with increase in the activity of synapse and the density of dendritic spine, through Sirt1. NRG1 signaling was prevented by administration of FGF2, which acts through the FGFR1 in MHE rats. Finally, intracerebroventricular injection with FGF2 or NRG1 mitigated the impairment of synaptogenesis.ConclusionThe data suggest that FGF2 may be a promising latent therapeutic reagent for MHE pathogenesis.

scholarly journals Fibroblast Growth Factor-2 Prevents Synaptic Pathology in Minimal Hepatic Encephalopathy via NRG1/ErbB4 Signaling

2020 ◽  
Author(s):  
Saidan Ding ◽  
Jian Wang ◽  
Weishan Zhuge ◽  
Yiru Ye ◽  
Xiaoai Lu ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Memory Function ◽  
Minimal Hepatic Encephalopathy ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Synaptic Pathology ◽  
Fgf2 Expression ◽  
Synaptic Formation

Abstract Minimal hepatic encephalopathy (MHE) is implicated in the impairment of memory function. Fibroblast growth factor-2 (FGF2) is involved in modulating synaptic and neuronal formation. The aim of this study is to examined the impacts of FGF2 on MHE pathology. Our study addressed whether FGF2 could trigger neuregulin1 (NRG1) release to ameliorate synaptic impairment in MHE rats and in primary cultured neurons. The results showed the decreased FGF2 expression in MHE brains. After treatment with FGF2, secreted neuregulin1 (NRG1) and ErbB4 were increased, and the interaction of the 2 proteins was enhanced. Additionally, treatment with FGF2 or NRG1 induced synaptic formation, with increase in the activity of synapse and the density of dendritic spine, through Sirt1.NRG1 signaling was prevented by administration of FGF2, which acts through the FGFR1 in MHE rats. Intracerebroventricular injection with FGF2 or NRG1 mitigated the impairment of synaptogenesis. The data suggest that FGF2 may be a promising latent therapeutic reagent for MHE pathogenesis.

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