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Toxicology. 2011 Apr 28;283(1):32-40. doi: 10.1016/j.tox.2011.01.026. Epub 2011 Feb 17.

Slit2-N inhibits PDGF-induced migration in rat airway smooth muscle cells: WASP and Arp2/3 involved.

Author information

1
Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Yangpu District, Shanghai 200433, PR China.

Abstract

BACKGROUND:

Slit2 has been reported to be implicated in many kinds of cell migration. However little is known about the effect of Slit2 on airway smooth muscle cell migration. This study was to detect the expression of Slit2 in rat airway smooth muscle (RASM) cells stimulated by platelet-derived growth factor (PDGF) and characterized the effect of Slit2-N on PDGF-induced migration of RASM cells in vitro.

METHODS:

mRNAs of Slit-Robo in RASM cells were examined by RT-PCR, and the effect of exogenous Slit2-N at different doses on PDGF-induced migration of RASM cells were examined by transwell and scrape-wound assays. Actin filaments (F-actin) were stained with rhodamine-conjugated phalloidin and the levels of protein expression were detected by western blot.

RESULTS:

RASM cells were identified to express Slit2, Slit3, Robo1, Robo2 and Robo4 in vitro. Slit2-N caused a time- and dose-dependent inhibition of cell proliferation, while had no significantly effect on cell apoptosis. Slit2-N pretreatment attenuated the elongated morphologic characteristics, reduced lamellipodia formation, inhibited actin rearrangement and cell migration induced by PDGF. PDGF-induced increase of WASP and Arp2/3 proteins were dramatically inhibited by 100 ng/ml Slit2-N.

CONCLUSION:

Slit2-N inhibits RASM cells migration at least partly through attenuating the expressions of WASP and Arp2/3, inhibiting actin rearrangement in vitro. The results contribute to provide new insights into the pathogenesis of airway remodeling in asthma and may be helpful for development of effective treatments.

PMID:
21315131
DOI:
10.1016/j.tox.2011.01.026
[Indexed for MEDLINE]

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