RGC-32 regulates reactive astrocytosis and extracellular matrix deposition in experimental autoimmune encephalomyelitis

Immunologic Research
Alexandru TatomirHorea Rus

Abstract

Extracellular matrix (ECM) deposition in active demyelinating multiple sclerosis (MS) lesions may impede axonal regeneration and can modify immune reactions. Response gene to complement (RGC)-32 plays an important role in the mediation of TGF-β downstream effects, but its role in gliosis has not been investigated. To gain more insight into the role played by RGC-32 in gliosis, we investigated its involvement in TGF-β-induced ECM expression and the upregulation of the reactive astrocyte markers α-smooth muscle actin (α-SMA) and nestin. In cultured neonatal rat astrocytes, collagens I, IV, and V, fibronectin, α-SMA, and nestin were significantly induced by TGF-β stimulation, and RGC-32 silencing resulted in a significant reduction in their expression. Using astrocytes isolated from RGC-32 knock-out (KO) mice, we found that the expression of TGF-β-induced collagens I, IV, and V, fibronectin, and α-SMA was significantly reduced in RGC-32 KO mice when compared with wild-type (WT) mice. SIS3 inhibition of Smad3 phosphorylation was also associated with a significant reduction in RGC-32 nuclear translocation and TGF-β-induced collagen I expression. In addition, during experimental autoimmune encephalomyelitis (EAE), RGC-32 KO mouse ast...Continue Reading

References

Apr 25, 2000·The EMBO Journal·J Massagué, D Wotton
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Dec 1, 2005·The Journal of Biological Chemistry·Shiyou ChenRobert J Lechleider
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Jan 24, 2009·Experimental and Molecular Pathology·Matthew FosbrinkHorea Rus
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Sep 25, 2012·Experimental and Molecular Pathology·Cosmin A TeglaHorea Rus
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Jan 9, 2014·Experimental and Molecular Pathology·Cosmin A TeglaHorea Rus
Jan 16, 2014·Experimental Neurology·Jared M CreggJerry Silver
Apr 2, 2014·Journal of Neuroscience Research·Maosheng Xia, Yue Zhu
Nov 9, 2014·Cold Spring Harbor Perspectives in Biology·Michael V Sofroniew
Mar 17, 2015·Experimental and Molecular Pathology·Cosmin A TeglaHorea Rus
Mar 31, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Violeta RusHorea G Rus
Dec 20, 2017·The Journal of Bone and Joint Surgery. American Volume·Diana ZhuRanjan Gupta

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Citations

Jun 30, 2019·Immunologic Research·Sonia I VlaicuHorea Rus
Jan 28, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Atefeh Rayatpour, Mohammad Javan
Feb 12, 2021·Frontiers in Immunology·Alexandru TatomirHorea Rus

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Methods Mentioned

BETA
co-immunoprecipitation
nuclear translocation
PCR
co-immunoprecipitation assay
co-IP
immunoprecipitation
nuclear

Software Mentioned

Graph Pad
IT
UN
SCAN

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