Epidermal CFTR Suppresses MAPK/NF-κB to Promote Cutaneous Wound Healing.
BACKGROUND
CFTR is implicated in cutaneous wound healing although the underlying mechanisms are not fully understood. In other cell types, CFTR is reported to regulate MAPK/ NF-κB signaling. We undertook the present study to explore a possible role of CFTR in regulating MAPK/NF-κB during cutaneous wound healing. Methods&amp; Results: The splint-excisional and incisional wound healing models were used in CFTR mutant (DF508) mice. The cell-scratch model was used in a human keratinocyte line, HaCaT, in conjunction with CFTR knockdown or overexpression. The epidermal inflammation, keratinocyte proliferation and differentiation, as well as MAPK/NF-κB signaling were examined. Inhibitors of MAPK/NF-κB were also used.


RESULTS
Both DF508 mice and HaCaT cells with CFTR knockdown exhibited delayed cutaneous wound healing with exuberant inflammation, increased proliferation and aberrant differentiation. Knockdown of CFTR in HaCaT cells resulted in phosphorylation of ERK, p38 and IκBα. The disturbance of inflammation, proliferation and differentiation in HaCaT cells were reversed by CFTR overexpression or inhibition of MAPK or NF-κB.


CONCLUSIONS
CFTR plays a role in suppressing MAPK/NF-κB to relieve inflammation, reduce proliferation and promote differentiation of keratinocytes, and thus promotes cutaneous wound healing.
State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Key Laboratory for Proteomics Disease, Institute of Burn Research, Southwest Hospital, the Third Military Medical University, Chongqing, China.
Jing
J
Chen
Yu
Y
Chen
Yajie
Y
Chen
Zicheng
Z
Yang
Bo
B
You
Ye Chun
YC
Ruan
Yizhi
Y
Peng
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing
D016328:NF-kappa B; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D020928:Mitogen-Activated Protein Kinases