title: Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts.
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 Ca(2+) concentration ([Ca(2+)]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, [Ca(2+)]i transiently increased in a strain-dependent manner. Hypotonic stress, which causes plasma membrane stretching, also transiently increased the [Ca(2+)]i. The stretch-induced [Ca(2+)]i elevation was attenuated in Ca(2+)-free solution. In contrast, the increase of [Ca(2+)]i by a 20% stretch was not inhibited by the inhibitor of stretch-activated channels GsMTx-4, Gd(3+), ruthenium red, or cytochalasin D. Cyclic stretching induced significant ATP releases from fibroblasts. However, the stretch-induced [Ca(2+)]i elevation was not inhibited by ATP diphosphohydrolase apyrase or a purinergic receptor antagonist suramin. Taken together, mechanical stretch induces Ca(2+) influx independently of conventional stretch-sensitive ion channels, the actin cytoskeleton, and released ATP.
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Murata
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. Electronic address: itori@med.nagoya-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.affiliation: Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Kishio
authors.initials: K
authors.lastname: Furuya
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Takahara
authors.affiliation: Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Okayama 700-8558, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Naruse
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Aso
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D013314:Stress, Mechanical
chemical_list: D000199:Actins; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: ARDS; ATP; Ca(2+) signaling; Idiopathic pulmonary fibrosis; Mechanical stress; Mechanotransduction