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Inhibition of P2X7 Alters Wound‐Induced Ca 2+ Mobilization and Cytoskeletal Rearrangements
Author(s) -
Minns Martin,
Teicher Gregory,
Rich Celeste,
TrinkausRandall Vickery
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.671.3
Subject(s) - purinergic receptor , membrane ruffling , microbiology and biotechnology , wound healing , cell migration , focal adhesion , receptor , signal transduction , calcium signaling , chemistry , biology , cell , cytoskeleton , immunology , biochemistry , extracellular
The process of wound healing involves a complex network of signaling pathways working to promote rapid migration and wound closure. Secreted nucleotides and purinergic receptors have been shown to play a major role in the calcium wave and subsequent calcium‐dependent signaling that is essential for proper healing. While the P2X7 purinergic receptor has been shown to promote migration, its exact role in this process is still relatively unknown. In this study, we show that P2X7 is down‐regulated after injury, but localizes to the leading edge of migrating corneal epithelium in organ culture. Inhibition of the P2X7 receptor prevents this leading‐edge localization and delays wound healing. In addition, we show that inhibition of P2X7 leads to an attenuated Ca 2+ mobilization and to a more rapid decline in the calcium wave after injury. In cell culture, inhibition of P2X7 results in fewer focal adhesion clusters and delayed migration. Live cell imaging reveals that P2X7 is required for membrane ruffling after scratch wounding. Together, these data demonstrate the importance of P2X7 in the early signaling events that promote epithelial cell migration.