Phospholipase C epsilon deficiency delays the early stage of cutaneous wound healing and attenuates scar formation in mice

摘要

This study aimed to investigate the role of phospholipase C epsilon (PLC epsilon) in the skin wound healing process. PLCe, an effect factor of Ras/Rap small G protein, plays a crucial role in skin inflammation by regulating inflammatory cytokines. Inflammatory responses are closely associated with wound healing. Full thickness skin wounds were made in the PLCe knockout (KO) and wild-type (WT) mice, and the healing process was analyzed. The macroscopic wound closure rate declined in the PLCe KO mice on days 3, 4, and 5 after wounding, following the decreased expression of interleukin (IL)-6, chemokine (C-X-C motif) ligand (Cxcl)-1, Cxcl-2, and chemokine (C-C motif) ligand (Ccl) 20. The proliferation rate of epidermal keratinocytes was not affected by PLCe, but silencing of PLC epsilon resulted in the delayed migration of keratinocytes. Moreover, the scars were found to be much smaller in the PLC epsilon KO mice than in the WT mice. The mRNA expression of Ccl20, collagen (Col) 6al, and Col17a1 decreased in the PLC epsilon KO mice. These results were in agreement with a previous hypothesis that PLC epsilon might delay the early stage of cutaneous wound healing by inhibiting the migration of keratinocytes, and decrease the expression of Col6al, Col17al, and Ccl20 by inhibiting the inflammatory response to reduce scar formation. This study shed light on a novel role of PLC epsilon in wound healing and provided new therapeutic approaches to target PLCe for diminishing scar formation after injury. (C) 2017 Elsevier Inc. All rights reserved.