Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts

Naohiko Murata, Satoru Ito, Kishio Furuya, Norihiro Takahara, Keiji Naruse, Hiromichi Aso, Masashi Kondo, Masahiro Sokabe, Yoshinori Hasegawa

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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 languageEnglish
Pages (from-to)101-105
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume453
Issue number1
DOIs
Publication statusPublished - 10-10-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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