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

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.

• Authors: Zhaohong Yin, Laura D Carbone, Mari Gotoh, Arnold Postlethwaite, Alyssa L Bolen, Gabor J Tigyi, Kimiko Murakami-Murofushi, Mitchell A Watsky
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 49 Issue 12 Pg. 2290-7 (Dec 2010) ISSN: 1462-0332 [Electronic] England
• PMID: 20823096 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Actins
• Chlorides
• Lysophospholipids
• lysophosphatidic acid

Topics

• Actins (metabolism)
• Adult
• Analysis of Variance
• Case-Control Studies
• Cells, Cultured
• Chlorides (metabolism)
• Female
• Fibroblasts (metabolism)
• Humans
• Lysophospholipids (metabolism)
• Male
• Middle Aged
• Muscle, Smooth (metabolism)
• Myofibroblasts (metabolism)
• Scleroderma, Systemic (metabolism)
• Skin (metabolism)