Lysophosphatidic acid-activated Cl- current activity in human systemic sclerosis skin fibroblasts

Zhaohong Yin, Laura D. Carbone, Mari Gotoh, Arnold Postlethwaite, Alyssa L. Bolen, Gabor J. Tigyi, Kimiko Murakami-murofushi, Mitchell A. Watsky

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Objectives: SSc (scleroderma) is an often fatal disease characterized by widespread tissue fibrosis. Fibroblasts play a key role in SSc-associated fibrosis. This study was designed to determine: (i) whether fibroblasts isolated from skin of patients with SSc have increased lysophosphatidic acid-activated Cl- current (IClLPA) activity vs healthy controls; (ii) whether myofibroblast differentiation is involved in SSc skin fibrosis; and (iii) whether SSc fibroblasts have different proliferation rates vs controls. Methods: Skin biopsies were taken from involved and uninvolved skin of SSc patients and controls. Whole-cell perforated patch-clamping was used to measure IClLPA activity in fibroblasts isolated and cultured from these biopsies. Western blotting was used to measure α-smooth muscle actin (α-SMA). Proliferation was measured using a colorimetric assay. Results: Fibroblasts cultured from SSc skin show significantly increased IClLPA activity following LPA exposure compared with control skin fibroblasts. α-SMA protein was significantly increased in cultured SSc skin fibroblasts vs controls. No significant differences in proliferation rates were found. Conclusions: Elevated IClLPA activity is a hallmark of SSc skin fibroblasts. Blocking IClLPA activation may be a new therapeutic approach for treating SSc-associated fibrosis.

Original languageEnglish (US)
Article numberkeq260
Pages (from-to)2290-2297
Number of pages8
JournalRheumatology
Volume49
Issue number12
DOIs
Publication statusPublished - Dec 1 2010
Externally publishedYes

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Keywords

  • Cl- channel
  • Fibroblast
  • Lysophosphatidic acid
  • Myofibroblast
  • α-Smooth muscle actin

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

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