{"doi":"10.3389/fimmu.2020.608294","title":"RGC-32 Regulates Generation of Reactive Astrocytes in Experimental Autoimmune Encephalomyelitis","abstract":"Astrocytes are increasingly recognized as critical contributors to multiple sclerosis pathogenesis. We have previously shown that lack of Response Gene to Complement 32 (RGC-32) alters astrocyte morphology in the spinal cord at the peak of experimental autoimmune encephalomyelitis (EAE), suggesting a role for RGC-32 in astrocyte differentiation. In this study, we analyzed the expression and distribution of astrocytes and astrocyte progenitors by immunohistochemistry in spinal cords of wild-type (WT) and RGC-32-knockout (KO) mice with EAE and of normal adult mice. Our analysis showed that during acute EAE, WT astrocytes had a reactive morphology and increased GFAP expression, whereas RGC-32 KO astrocytes had a morphology similar to that of radial glia and an increased expression of progenitor markers such as vimentin and fatty acid binding protein 7 (FABP7). In control mice, GFAP expression and astrocyte density were also significantly higher in the WT group, whereas the number of vimentin and FABP7-positive radial glia was significantly higher in the RGC-32 KO group. In vitro studies on cultured neonatal astrocytes from WT and RGC-32 KO mice showed that RGC-32 regulates a complex array of molecular networks pertaining to signal transduction, growth factor expression and secretion, and extracellular matrix (ECM) remodeling. Among the most differentially expressed factors were insulin-like growth factor 1 (IGF1), insulin-like growth factor binding proteins (IGFBPs), and connective tissue growth factor (CTGF); their expression was downregulated in RGC-32-depleted astrocytes. The nuclear translocation of STAT3, a transcription factor critical for astrogliogenesis and driving glial scar formation, was also impaired after RGC-32 silencing. Taken together, these data suggest that RGC-32 is an important regulator of astrocyte differentiation during EAE and that in the absence of RGC-32, astrocytes are unable to fully mature and become reactive astrocytes.","journal":"Frontiers in Immunology","year":2021,"id":203231,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":367766,"name":"Austin Beltrand","orcid":null,"position":1,"is_corresponding":false},{"id":246498,"name":"Vinh Nguyen","orcid":"0000-0003-2462-9594","position":2,"is_corresponding":false},{"id":367765,"name":"Dallas Boodhoo","orcid":null,"position":3,"is_corresponding":false},{"id":783947,"name":"Armugam P. Mekala","orcid":"0000-0001-7142-3594","position":4,"is_corresponding":false},{"id":342097,"name":"Cornelia Cudrici","orcid":"0000-0002-9077-8195","position":5,"is_corresponding":false},{"id":449008,"name":"Tudor C. Badea","orcid":"0000-0003-3086-6713","position":6,"is_corresponding":false},{"id":360709,"name":"Dafin F. Mureșanu","orcid":"0000-0002-9536-1153","position":7,"is_corresponding":false},{"id":297015,"name":"Violeta Rus","orcid":null,"position":8,"is_corresponding":false},{"id":366081,"name":"Horea Rus","orcid":"0000-0003-2415-5130","position":9,"is_corresponding":false},{"id":366078,"name":"Alexandru Tatomir","orcid":"0000-0003-2674-3278","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:14.206397Z","pmid":"33569054","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}