Abstract
One cause of progressive pulmonary fibrosis is dysregulated wound healing after lung inflammation or damage in patients with idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome. The mechanical forces are considered to regulate pulmonary fibrosis via activation of lung fibroblasts. In this study, the effects of mechanical stretch on the intracellular Ca2+ concentration ([Ca2+]i) and ATP release were investigated in primary human lung fibroblasts. Uniaxial stretch (10-30% in strain) was applied to fibroblasts cultured in a silicone chamber coated with type I collagen using a stretching apparatus. Following stretching and subsequent unloading, [Ca2+]i transiently increased in a strain-dependent manner. Hypotonic stress, which causes plasma membrane stretching, also transiently increased the [Ca2+]i. The stretch-induced [Ca2+]i elevation was attenuated in Ca2+-free solution. In contrast, the increase of [Ca2+]i by a 20% stretch was not inhibited by the inhibitor of stretch-activated channels GsMTx-4, Gd3+, ruthenium red, or cytochalasin D. Cyclic stretching induced significant ATP releases from fibroblasts. However, the stretch-induced [Ca2+]i elevation was not inhibited by ATP diphosphohydrolase apyrase or a purinergic receptor antagonist suramin. Taken together, mechanical stretch induces Ca2+ influx independently of conventional stretch-sensitive ion channels, the actin cytoskeleton, and released ATP.
| Original language | English |
|---|---|
| Pages (from-to) | 101-105 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 453 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Oct 10 2014 |
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Keywords
- ARDS
- ATP
- Ca signaling
- Idiopathic pulmonary fibrosis
- Mechanical stress
- Mechanotransduction
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Molecular Biology
- Medicine(all)
Cite this
Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts. / Murata, Naohiko; Ito, Satoru; Furuya, Kishio; Takahara, Norihiro; Naruse, Keiji; Aso, Hiromichi; Kondo, Masashi; Sokabe, Masahiro; Hasegawa, Yoshinori.
In: Biochemical and Biophysical Research Communications, Vol. 453, No. 1, 10.10.2014, p. 101-105.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts
AU - Murata, Naohiko
AU - Ito, Satoru
AU - Furuya, Kishio
AU - Takahara, Norihiro
AU - Naruse, Keiji
AU - Aso, Hiromichi
AU - Kondo, Masashi
AU - Sokabe, Masahiro
AU - Hasegawa, Yoshinori
PY - 2014/10/10
Y1 - 2014/10/10
N2 - One cause of progressive pulmonary fibrosis is dysregulated wound healing after lung inflammation or damage in patients with idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome. The mechanical forces are considered to regulate pulmonary fibrosis via activation of lung fibroblasts. In this study, the effects of mechanical stretch on the intracellular Ca2+ concentration ([Ca2+]i) and ATP release were investigated in primary human lung fibroblasts. Uniaxial stretch (10-30% in strain) was applied to fibroblasts cultured in a silicone chamber coated with type I collagen using a stretching apparatus. Following stretching and subsequent unloading, [Ca2+]i transiently increased in a strain-dependent manner. Hypotonic stress, which causes plasma membrane stretching, also transiently increased the [Ca2+]i. The stretch-induced [Ca2+]i elevation was attenuated in Ca2+-free solution. In contrast, the increase of [Ca2+]i by a 20% stretch was not inhibited by the inhibitor of stretch-activated channels GsMTx-4, Gd3+, ruthenium red, or cytochalasin D. Cyclic stretching induced significant ATP releases from fibroblasts. However, the stretch-induced [Ca2+]i elevation was not inhibited by ATP diphosphohydrolase apyrase or a purinergic receptor antagonist suramin. Taken together, mechanical stretch induces Ca2+ influx independently of conventional stretch-sensitive ion channels, the actin cytoskeleton, and released ATP.
AB - One cause of progressive pulmonary fibrosis is dysregulated wound healing after lung inflammation or damage in patients with idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome. The mechanical forces are considered to regulate pulmonary fibrosis via activation of lung fibroblasts. In this study, the effects of mechanical stretch on the intracellular Ca2+ concentration ([Ca2+]i) and ATP release were investigated in primary human lung fibroblasts. Uniaxial stretch (10-30% in strain) was applied to fibroblasts cultured in a silicone chamber coated with type I collagen using a stretching apparatus. Following stretching and subsequent unloading, [Ca2+]i transiently increased in a strain-dependent manner. Hypotonic stress, which causes plasma membrane stretching, also transiently increased the [Ca2+]i. The stretch-induced [Ca2+]i elevation was attenuated in Ca2+-free solution. In contrast, the increase of [Ca2+]i by a 20% stretch was not inhibited by the inhibitor of stretch-activated channels GsMTx-4, Gd3+, ruthenium red, or cytochalasin D. Cyclic stretching induced significant ATP releases from fibroblasts. However, the stretch-induced [Ca2+]i elevation was not inhibited by ATP diphosphohydrolase apyrase or a purinergic receptor antagonist suramin. Taken together, mechanical stretch induces Ca2+ influx independently of conventional stretch-sensitive ion channels, the actin cytoskeleton, and released ATP.
KW - ARDS
KW - ATP
KW - Ca signaling
KW - Idiopathic pulmonary fibrosis
KW - Mechanical stress
KW - Mechanotransduction
UR - http://www.scopus.com/inward/record.url?scp=84908364301&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908364301&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2014.09.063
DO - 10.1016/j.bbrc.2014.09.063
M3 - Article
C2 - 25256743
AN - SCOPUS:84908364301
VL - 453
SP - 101
EP - 105
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -