Another recent report has shown that calcium signaling is involved in wound closure in zebrafish larvae.37 Although the detailed mechanism is not clear, but the authors suggest that in zebrafish, the two calcium channels, Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+ ATPase (PMCA), are involved in wound repair. An NCX inhibitor, but not a PMCA inhibitor, impairs wound closure, which is consistent with a role for NCX rather than PMCA in wound repair. NCX and PMCA are important for calcium homeostasis, but these channels have also been reported to be involved in wound repair (Figure 1).8, 38 First, calcium channels could be involved in sensing of the chemical environment by allowing for regulation of the receptors (e.g., EGFR and LPA receptors) on the plasma membrane of epithelial cells. Second, calcium channels could be used to generate calcium-dependent second messengers that promote wound repair. For example, phospholipase C (PLC) is activated by the Ca2+-dependent receptor to phosphorylate phosphatidylinositol 4,5-bisphosphate (PIP2) in the membrane of epithelial cells to form diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), both of which activate protein kinase C (PKC) that is important in cell migration.9, 39, 40 Third, calcium channels could be used to generate calcium-dependent second messengers that regulate protein function. One example is the generation of inositol 1,4,5-trisphosphate (IP3) by the activation of phospholipase C, which is important in calcium-induced IP3-receptor signaling and regulation of the actin cytoskeleton.40 Another example is the generation of nitric oxide (NO) by activation of inducible nitric oxide synthase (iNOS) by calcium signaling.41 Finally, calcium influx is also important in the activation of the proteins involved in cell proliferation. Thus, the role of calcium signaling in wound repair is an important area for future studies.
Wound healing is a dynamic process that involves the proliferation, migration, and contraction of the epidermal layer, the movement of epithelial cells to cover the wound area, and the organization of an extracellular matrix to restore the integrity of the epidermis. 827ec27edc