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Myofibroblast differentiation and its functional properties are inhibited by
nicotine and e-cigarette via mitochondrial OXPHOS complex III
#MMPMID28256533
Lei W
; Lerner C
; Sundar IK
; Rahman I
Sci Rep
2017[Mar]; 7
(?): 43213
PMID28256533
show ga
Nicotine is the major stimulant in tobacco products including e-cigarettes.
Fibroblast to myofibroblast differentiation is a key process during wound healing
and is dysregulated in lung diseases. The role of nicotine and e-cigarette
derived nicotine on cellular functions including profibrotic response and other
functional aspects is not known. We hypothesized that nicotine and e-cigarettes
affect myofibroblast differentiation, gel contraction, and wound healing via
mitochondria stress through nicotinic receptor-dependent mechanisms. To test the
hypothesis, we exposed human lung fibroblasts with various doses of nicotine and
e-cigarette condensate and determined myofibroblast differentiation,
mitochondrial oxidative phosphorylation (OXPHOS), wound healing, and gel
contraction at different time points. We found that both nicotine and e-cigarette
inhibit myofibroblast differentiation as shown by smooth muscle actin and
collagen type I, alpha 1 abundance. Nicotine and e-cigarette inhibited OXPHOS
complex III accompanied by increased MitoROS, and this effect was augmented by
complex III inhibitor antimycin A. These mitochondrial associated effects by
nicotine resulted in inhibition of myofibroblast differentiation. These effects
were associated with inhibition of wound healing and gel contraction suggesting
that nicotine is responsible for dysregulated repair during injurious responses.
Thus, our data suggest that nicotine causes dysregulated repair by inhibition of
myofibroblast differentiation via OXPHOS pathway.
|Cell Differentiation/*drug effects
[MESH]
|Cells, Cultured
[MESH]
|Electron Transport Complex III/*antagonists & inhibitors
[MESH]
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