Wound closure and wound management: A new therapeutic molecular target

Abstract

Wound closure and infection control are the primary goal of wound management. A variety of disinfectants and antimicrobial agents are widely available today and routinely achieve infection control. On the contrary, wound closure still remains a challenging goal. Cell adhesion, migration and contraction play significant roles in creating contractile force of patent wound margins and in contributing to wound closure. Modulations of these cellular behaviors have been investigated in the context of wound contraction; however, therapeutic strategy to achieve wound closure has not been established. Recently, we have reported that a previously unknown cytoskeleton molecule, wound inducible transcript-3.0 (wit3.0) also known as fibroblast growth factor receptor 1 oncogene partner 2 (FGFR1OP2), can significantly modulate fibroblast-driven wound closure in vitro and in vivo. The dynamic role of cytoskeleton in different experimental models may provide a novel platform for designing the therapeutic target of wound management.

Figure 1

Expression of FGFR1OP2/wit3.0 in rat primary oral and skin fibroblasts. (A) Immunocytological staining identified FGFR1OP2/wit3.0 (green) amorphously in the cytoplasma surrounding nucleus (DAPI: blue) of oral and skin fibroblasts. In oral fibroblasts derived from gingiva of post-tooth extraction wounding, FGFR1OP2/wit3.0 localized in cytoskeletal network containing F-actin (red). In contrast, skin fibroblasts harvested after excisional wounding showed no change in FGFR1OP2/wit3.0 distribution. (Confocal laser scanning micrographs of oral fibroblasts are reproduced from Lin et al., Am J Pathol, 2010, 176:108–121, with permission.) (B) The steady state mRN A levels of FGFR1OP2/wit3.0 and alpha smooth muscle actin (α-SM actin) were characterized by real time reverse transcription polymerase chain reaction. Wounded oal and skin fibroblasts demonstrated the increase in a-SM actin expression, albeit at different magnitudes. In oral fibroblasts, wounding increased the expression of FGFR1OP2/wit3.0 expression; whereas wounding did not modulate its expression in skin fibroblasts.