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Modulation of proteoglycan receptor PTPσ enhances MMP-2 activity to promote recovery from multiple sclerosis

Author

Listed:
  • Fucheng Luo

    (Case Western Reserve University School of Medicine)

  • Amanda Phuong Tran

    (Case Western Reserve University School of Medicine)

  • Li Xin

    (Case Western Reserve University School of Medicine)

  • Chandrika Sanapala

    (Case Western Reserve University School of Medicine)

  • Bradley T. Lang

    (BioEnterprise)

  • Jerry Silver

    (Case Western Reserve University School of Medicine)

  • Yan Yang

    (Case Western Reserve University School of Medicine
    Case Western Reserve University School of Medicine)

Abstract

Multiple Sclerosis (MS) is characterized by focal CNS inflammation leading to the death of oligodendrocytes (OLs) with subsequent demyelination, neuronal degeneration, and severe functional deficits. Inhibitory chondroitin sulfate proteoglycans (CSPGs) are increased in the extracellular matrix in the vicinity of MS lesions and are thought to play a critical role in myelin regeneration failure. We here show that CSPGs curtail remyelination through binding with their cognate receptor, protein tyrosine phosphatase σ (PTPσ) on oligodendrocyte progenitor cells (OPCs). We report that inhibition of CSPG/PTPσ signaling by systemically deliverable Intracellular Sigma Peptide (ISP), promotes OPC migration, maturation, remyelination, and functional recovery in animal models of MS. Furthermore, we report a downstream molecular target of PTPσ modulation in OPCs involving upregulation of the protease MMP-2 that allows OPCs to enzymatically digest their way through CSPGs. In total, we demonstrate a critical role of PTPσ/CSPG interactions in OPC remyelination in MS.

Suggested Citation

  • Fucheng Luo & Amanda Phuong Tran & Li Xin & Chandrika Sanapala & Bradley T. Lang & Jerry Silver & Yan Yang, 2018. "Modulation of proteoglycan receptor PTPσ enhances MMP-2 activity to promote recovery from multiple sclerosis," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06505-6
    DOI: 10.1038/s41467-018-06505-6
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    Cited by:

    1. Samira Ghorbani & Emily Jelinek & Rajiv Jain & Benjamin Buehner & Cenxiao Li & Brian M. Lozinski & Susobhan Sarkar & Deepak K. Kaushik & Yifei Dong & Thomas N. Wight & Soheila Karimi-Abdolrezaee & Gee, 2022. "Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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