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2017 ; 5
(9
): ä Nephropedia Template TP
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Matrix stiffness regulates migration of human lung fibroblasts
#MMPMID28507166
Asano S
; Ito S
; Takahashi K
; Furuya K
; Kondo M
; Sokabe M
; Hasegawa Y
Physiol Rep
2017[May]; 5
(9
): ä PMID28507166
show ga
In patients with pulmonary diseases such as idiopathic pulmonary fibrosis and
severe acute respiratory distress syndrome, progressive pulmonary fibrosis is
caused by dysregulated wound healing via activation of fibroblasts after lung
inflammation or severe damage. Migration of fibroblasts toward the fibrotic
lesions plays an important role in pulmonary fibrosis. Fibrotic tissue in the
lung is much stiffer than normal lung tissue. Emerging evidence supports the
hypothesis that the stiffness of the matrix is not only a consequence of
fibrosis, but also can induce fibroblast activation. Nevertheless, the effects of
substrate rigidity on migration of lung fibroblasts have not been fully
elucidated. We evaluated the effects of substrate stiffness on the morphology,
?-smooth muscle actin (?-SMA) expression, and cell migration of primary human
lung fibroblasts by using polyacrylamide hydrogels with stiffnesses ranging from
1 to 50 kPa. Cell motility was assessed by platelet-derived growth factor
(PDGF)-induced chemotaxis and random walk migration assays. As the stiffness of
substrates increased, fibroblasts became spindle-shaped and spread. Expression of
?-SMA proteins was higher on the stiffer substrates (25 kPa gel and plastic
dishes) than on the soft 2 kPa gel. Both PDGF-induced chemotaxis and random walk
migration of fibroblasts precultured on stiff substrates (25 kPa gel and plastic
dishes) were significantly higher than those of cells precultured on 2 kPa gel.
Transfection of the fibroblasts with short interfering RNA for ?-SMA inhibited
cell migration. These findings suggest that fibroblast activation induced by a
stiff matrix is involved in mechanisms of the pathophysiology of pulmonary
fibrosis.