Project description:We recently demonstrated that the ‘Metabesity’ factor HMG20A is essential for beta cell functional maturity and adaptation to physiological stress. As this chromatin remodeling factor also dictates CNS development, we sought to determine whether HMG20A is expressed in astrocytes and whether it potentiates astrocyte function in response to environmental cues. To investigate the function and regulatory mechanism of HMG20A, RNA-seq was performed on astrocytes treated or not with a siHMG20A. HMG20A silencing in astrocytes resulted in repression of pro-inflammatory, cholesterol homeostasis and epithelial-to-mesenchymal transition pathways. This results indicate that HMG20A coordinates the astrocyte polarization state. Under physiological pressure such as obesity and insulin resistance that induces low grade inflammation, HMG20A expression is increased to induce astrogliosis in an attempt to preserve the neuronal network and glucose homeostasis. onetheless, a chronic metabesity state or functional mutations will result in lower levels of HMG20A, failure to promote astrogliosis and increase susceptibility of neurons to stress-mediated apoptosis.
Project description:In a previous study performed in our laboratory, the level of FGF1 RNA was found to be increased in remyelinated multiple sclerosis lesions compared to control brain (unpublished observation). Astrocytes play a key role in multiple sclerosis lesion formation. To shed light on potential FGF1-mediated functions in multiple sclerosis, the impact of FGF1 on astrocytes was investigated.