Abstract
N-formyl peptide receptors (FPRs) serve as phagocyte pattern-recognition receptors that play a crucial role in the regulation of host defense against infection. Epithelial cells also express FPRs, and their activation during inflammation or injury results in enhanced epithelial migration and proliferation and improved mucosal wound repair. However, signaling mechanisms that govern epithelial FPR1 activity are not well understood. This study identified a novel FPR1-interacting protein, WD40 repeat protein (WDR)-26, which negatively regulates FPR1-mediated wound healing in intestinal epithelial cells. We show that WDR26-mediated inhibition of wound repair is mediated through the inhibition of Rac family small GTPase 1 and cell division cycle 42 activation, as well as downstream intracellular reactive oxygen species production. Furthermore, on FPR1 activation with N-formyl-methionyl-leucyl phenylalanine, WDR26 dissociates from FPR1, resulting in the activation of downstream cell division cycle 42/Rac family small GTPase 1 signaling, increased epithelial cell migration, and mucosal wound repair. These findings elucidate a novel regulatory function of WDR26 in FPR1-mediated wound healing in intestinal epithelial cells.