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The Use of Connexin-Based Therapeutic Approaches to Target Inflammatory Diseases

  • Simon J. O’Carroll
  • David L. Becker
  • Joanne O. Davidson
  • Alistair J. Gunn
  • Louise F. B. Nicholson
  • Colin R. Green
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1037)

Abstract

Alterations in Connexin43 (Cx43) expression levels have been shown to play a role in inflammatory processes including skin wounding and neuroinflammation. Cx43 protein levels increase following a skin wound and can inhibit wound healing. Increased Cx43 has been observed following stroke, epilepsy, ischemia, optic nerve damage, and spinal cord injury with gap junctional communication and hemichannel opening leading to increased secondary damage via the inflammatory response. Connexin43 modulation has been identified as a potential target for protection and repair in neuroinflammation and skin wound repair. This review describes the use of a Cx43 specific antisense oligonucleotide (Cx43 AsODN) and peptide mimetics of the connexin extracellular loop domain to modulate Cx43 expression and/or function in inflammatory disorders of the skin and central nervous system. An overview of the role of connexin43 in inflammatory conditions, how antisense and peptide have allowed us to elucidate the role of Cx43 in these diseases, create models of diseases to test interventions and their potential for use clinically or in current clinical trials is presented. Antisense oligonucleotides are applied topically and have been used to improve wound healing following skin injury. They have also been used to develop ex vivo models of neuroinflammatory diseases that will allow testing of intervention strategies. The connexin mimetic peptides have shown potential in a number of neuroinflammatory disorders in ex vivo models as well as in vivo when delivered directly to the injury site or when delivered systemically.

Key words

Connexin Antisense Mimetic peptide Inflammation Wound healing 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Simon J. O’Carroll
    • 1
  • David L. Becker
    • 2
  • Joanne O. Davidson
    • 3
  • Alistair J. Gunn
    • 3
  • Louise F. B. Nicholson
    • 1
  • Colin R. Green
    • 4
  1. 1.Department of Anatomy with Radiology, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
  2. 2.Department of Cell and Developmental BiologyUniversity College LondonLondonUK
  3. 3.Department of PhysiologyUniversity of AucklandAucklandNew Zealand
  4. 4.Department of Ophthalmology, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand

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