RGC-32 regulates nuclear factor I-A and reactive astrocytes during experimental autoimmune encephalomyelitis 2267

Abstract Description Reactive astrocytes play a crucial role in the pathogenesis of multiple sclerosis (MS). Nuclear factor I-A (NFIA) is a transcription factor that plays a central part in astrocyte development. Our goal was to better characterize the role of the RGC-32/NFIA pathway in reactive astrocytes. Spinal cords from WT and RGC-32 KO mice with EAE were stained for glial fibrillary acidic protein (GFAP), vimentin, fatty acid binding protein 7 (FABP7), NFIA, and for STAT3 expression. Lack of RGC-32 had a significant impact on the transcriptomic programs in astrocytes, affecting the expression of NFIA in these cells. During acute EAE, we found a significant increase of NFIA+ radial glial cells in RGC-32 KO mice. A lower number of NFIA+-reactive astrocytes was found in RGC-32 KO mice with acute EAE compared to WT mice. Additionally, during acute EAE, WT reactive astrocytes showed an increased GFAP expression, whereas RGC-32 KO astrocytes displayed an increased expression of progenitor markers such as vimentin and FABP7. We next investigated the expression of STAT3 and found an increased number of STAT3-expressing astrocytes in WT mice as compared to RGC-32 KO mice. siRNA silencing of RGC-32 expression in astrocytes resulted in impaired nuclear translocation of STAT3. These findings suggest that RGC-32’s regulation of NFIA may be involved in facilitation of reactive astrogliosis. The RGC-32-NFIA-STAT3 axis may be a new target for modulating astrocyte differentiation in MS. Funding Sources Veterans Administration Funding Merit Award (I01BX001458) Topic Categories Immune Mechanisms of Human Disease (HUM)