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 Aaron Watsky

Research output: Contribution to journalArticle

18 Citations (Scopus)

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
StatePublished - Dec 1 2010
Externally publishedYes

Fingerprint

Systemic Scleroderma
Human Activities
Fibroblasts
Skin
Fibrosis
Biopsy
Myofibroblasts
lysophosphatidic acid
Constriction
Smooth Muscle
Actins
Western Blotting

Keywords

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

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Lysophosphatidic acid-activated Cl- current activity in human systemic sclerosis skin fibroblasts. / Yin, Zhaohong; Carbone, Laura D; Gotoh, Mari; Postlethwaite, Arnold; Bolen, Alyssa L.; Tigyi, Gabor J.; Murakami-murofushi, Kimiko; Watsky, Mitchell Aaron.

In: Rheumatology, Vol. 49, No. 12, keq260, 01.12.2010, p. 2290-2297.

Research output: Contribution to journalArticle

Yin, Z, Carbone, LD, Gotoh, M, Postlethwaite, A, Bolen, AL, Tigyi, GJ, Murakami-murofushi, K & Watsky, MA 2010, 'Lysophosphatidic acid-activated Cl- current activity in human systemic sclerosis skin fibroblasts', Rheumatology, vol. 49, no. 12, keq260, pp. 2290-2297. https://doi.org/10.1093/rheumatology/keq260
Yin, Zhaohong ; Carbone, Laura D ; Gotoh, Mari ; Postlethwaite, Arnold ; Bolen, Alyssa L. ; Tigyi, Gabor J. ; Murakami-murofushi, Kimiko ; Watsky, Mitchell Aaron. / Lysophosphatidic acid-activated Cl- current activity in human systemic sclerosis skin fibroblasts. In: Rheumatology. 2010 ; Vol. 49, No. 12. pp. 2290-2297.
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