RGC-32 Acts as a Hub to Regulate the Transcriptomic Changes Associated With Astrocyte Development and Reactive Astrocytosis.

Autor:	Tatomir A; Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, United States.; Department of Neurosciences, 'Iuliu Hatieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania., Beltrand A; Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, United States., Nguyen V; Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland, School of Medicine, Baltimore, MD, United States., Courneya JP; Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, United States., Boodhoo D; Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, United States., Cudrici C; Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States., Muresanu DF; Department of Neurosciences, 'Iuliu Hatieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania., Rus V; Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland, School of Medicine, Baltimore, MD, United States., Badea TC; Retinal Circuit Development and Genetics Unit, N-NRL, National Eye Institute, Bethesda, MD, United States.; Research and Development Institute, Faculty of Medicine, Transylvania University of Brasov, Brasov, Romania., Rus H; Department of Neurology, University of Maryland, School of Medicine, Baltimore, MD, United States.; Research Service, Veterans Administration Maryland Health Care System, Baltimore, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Jul 29; Vol. 12, pp. 705308. Date of Electronic Publication: 2021 Jul 29 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.705308
Abstrakt:	Response Gene to Complement 32 (RGC-32) is an important mediator of the TGF-β signaling pathway, and an increasing amount of evidence implicates this protein in regulating astrocyte biology. We showed recently that spinal cord astrocytes in mice lacking RGC-32 display an immature phenotype reminiscent of progenitors and radial glia, with an overall elongated morphology, increased proliferative capacity, and increased expression of progenitor markers when compared to their wild-type (WT) counterparts that make them incapable of undergoing reactive changes during the acute phase of experimental autoimmune encephalomyelitis (EAE). Here, in order to decipher the molecular networks underlying RGC-32's ability to regulate astrocytic maturation and reactivity, we performed next-generation sequencing of RNA from WT and RGC-32 knockout (KO) neonatal mouse brain astrocytes, either unstimulated or stimulated with the pleiotropic cytokine TGF-β. Pathway enrichment analysis showed that RGC-32 is critical for the TGF-β-induced up-regulation of transcripts encoding proteins involved in brain development and tissue remodeling, such as axonal guidance molecules, transcription factors, extracellular matrix (ECM)-related proteins, and proteoglycans. Our next-generation sequencing of RNA analysis also demonstrated that a lack of RGC-32 results in a significant induction of WD repeat and FYVE domain-containing protein 1 (Wdfy1) and stanniocalcin-1 (Stc1). Immunohistochemical analysis of spinal cords isolated from normal adult mice and mice with EAE at the peak of disease showed that RGC-32 is necessary for the in vivo expression of ephrin receptor type A7 in reactive astrocytes, and that the lack of RGC-32 results in a higher number of homeodomain-only protein homeobox (HOPX) + and CD133 + radial glia cells. Collectively, these findings suggest that RGC-32 plays a major role in modulating the transcriptomic changes in astrocytes that ultimately lead to molecular programs involved in astrocytic differentiation and reactive changes during neuroinflammation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Tatomir, Beltrand, Nguyen, Courneya, Boodhoo, Cudrici, Muresanu, Rus, Badea and Rus.)
Databáze:	MEDLINE
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