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2016 ; 311
(5
): L893-L902
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Focal adhesion kinase (FAK) and mechanical stimulation negatively regulate the
transition of airway smooth muscle tissues to a synthetic phenotype
#MMPMID27612967
Wu Y
; Huang Y
; Gunst SJ
Am J Physiol Lung Cell Mol Physiol
2016[Nov]; 311
(5
): L893-L902
PMID27612967
show ga
The effects of mechanical forces and focal adhesion kinase (FAK) in regulating
the inflammatory responses of airway smooth muscle (ASM) tissues to stimulation
with interleukin (IL)-13 were investigated. Canine tracheal tissues were
subjected to different mechanical loads in vitro, and the effects of mechanical
load on eotaxin secretion and inflammatory signaling pathways in response to
IL-13 were determined. Eotaxin secretion by tissues in response to IL-13 was
significantly inhibited in muscles maintained at a higher (+) load compared with
those at a lower (-) load as assessed by ELISA, and Akt activation was also
reduced in the higher (+) loaded tissues. Conversely the (+) mechanical load
increased activation of the focal adhesion proteins FAK and paxillin in the
tissues. The role of FAK in regulating the mechanosensitive responses was
assessed by overexpressing FAK-related nonkinase in the tissues, by expressing
the FAK kinase-dead mutant FAK Y397F, or by treating tissues with the FAK
inhibitor PF-573228. FAK inactivation potentiated Akt activity and increased
eotaxin secretion in response to IL-13. FAK inhibition also suppressed the
mechanosensitivity of Akt activation and eotaxin secretion. In addition, FAK
inactivation suppressed smooth muscle myosin heavy chain expression induced by
the higher (+) mechanical load. The results demonstrate that the imposition of a
higher mechanical load on airway smooth muscle stimulates FAK activation, which
promotes the expression of the differentiated contractile phenotype and
suppresses the synthetic phenotype and the inflammatory responses of the muscle
tissue.