Connexin 43 regulates astrocytic migration and proliferation in response to injury

Benjaporn Homkajorn, Neil Sims, Hakan Muyderman

    Research output: Contribution to journalArticlepeer-review

    31 Citations (Scopus)

    Abstract

    Marked alterations in astrocyte function are a universal response to disease or injury in the central nervous system. Affected astrocytes develop characteristic morphological changes known as "reactive astrogliosis", characterized by increased expression of the intermediate filament proteins, glial fibrillary acidic protein and vimentin. Reactive astrocytes also display alterations in other proteins including a rapid up-regulation of the gap junction protein, Connexin 43. The present study tests whether Connexin 43 is directly involved in the astrocytic response to injury. We have down regulated Connexin 43 expression using a microRNA generating plasmid and investigated the functional consequences of this treatment on the response of astrocytes in primary culture to a well-characterized scratch wound injury. The treatment resulted in more than 70% transfection efficiency and a near complete depletion of Connexin 43 in transfected cells. Compared to cells transfected with non-targeting microRNA, the cells depleted of Connexin 43 showed a slower wound closure and fewer transfected cells in the wound area. These changes were associated with decreased proliferation of the Connexin 43-depleted cells as well as shorter processes extending into the wound area suggesting a direct impairment of migration. The effects were independent of gap junction conductivity as exposure to the gap junction blocker carbenoxolone did not affect the rate of wound healing. The findings directly indicate a role for Connexin 43 in the astrocytic response to injury and suggest that modification of Connexin 43 expression might provide a therapeutic target to alter potentially deleterious astrocytic responses.

    Original languageEnglish
    Pages (from-to)197-201
    Number of pages5
    JournalNeuroscience Letters
    Volume486
    Issue number3
    DOIs
    Publication statusPublished - 17 Dec 2010

    Keywords

    • Astrocytes
    • Connexin 43
    • Nucleofection
    • Scratch wound

    Fingerprint Dive into the research topics of 'Connexin 43 regulates astrocytic migration and proliferation in response to injury'. Together they form a unique fingerprint.

    Cite this