Nicotine inhibits human gingival fibroblast migration via modulation of Rac signalling pathways.
OBJECTIVE
Cigarette smoking is a risk factor in the development of periodontal diseases. In addition, a delayed healing process has been shown in smokers compared with non-smokers after periodontal treatment. Cell migration is a key process of wound healing and it is highly regulated by a variety of signalling pathways. The small G protein, Rac, is necessary for cell migration. Our aim was to determine if nicotine disrupted Rac and its downstream signalling proteins, p21-activated kinase 1/2 (PAK1/2), and p44/42 mitogen-activated protein kinase (MAPK) (extracellular regulated kinase 1/2).


METHODS
Primary human fibroblasts from healthy gingival tissues were cultured and grown to confluence. Cells were serum starved for 24 h, and then treated with nicotine (0 or 0.5 microM) prior to in vitro wounding. Cell migration was analysed in live cell assays following in vitro wounds. Rac activity, phosphorylation levels of PAK1/2, and p44/42 MAPK were assessed in cultures treated with or without nicotine after multiple wounds.


RESULTS
Nicotine decreased cell migration rates by 50% compared with controls. In addition, nicotine altered the activation patterns of Rac and PAK 1/2 and up-regulated p44/42 MAPK.


CONCLUSIONS
Decreased cell migration in periodontal wounds exposed to nicotine may be mediated through the Rac and PAK1/2 signalling pathways.
Fang
Yiyu
Y
Biomedical Sciences Department, Texas A&M University System, Health Science Center, Baylor College of Dentistry, Dallas, TX, USA.
Svoboda
Kathy K H
KK
D000704:Analysis of Variance; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005881:Gingiva / Q000187:drug effects / Q000293:injuries; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism
D018722:Nicotinic Agonists; D009538:Nicotine; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020744:rac GTP-Binding Proteins