Nogo-B regulates migration and contraction of airway smooth muscle cells by decreasing ARPC 2-3 and increasing MYL-9 expressionReport as inadecuate

Nogo-B regulates migration and contraction of airway smooth muscle cells by decreasing ARPC 2-3 and increasing MYL-9 expression - Download this document for free, or read online. Document in PDF available to download.

Respiratory Research

, 12:14

First Online: 01 December 2011Received: 16 September 2010Accepted: 21 January 2011


BackgroundAbnormal proliferation, apoptosis, migration and contraction of airway smooth muscle ASM cells in airway remodeling in asthma are basically excessive repair responses to a network of inflammatory mediators such as PDGF, but the mechanisms of such responses remain unclear. Nogo-B, a member of the reticulum family 4RTN4, is known to play a key role in arteriogenesis and tissue repair. Further studies are needed to elucidate the role of Nogo-B in airway smooth muscle abnormalities.

MethodsA mouse model of chronic asthma was established by repeated OVA inhalation and subjected to Nogo-B expression analysis using immunohistochemistry and Western Blotting. Then, primary human bronchial smooth muscle cells HBSMCs were cultured in vitro and a siRNA interference was performed to knockdown the expression of Nogo-B in the cells. The effects of Nogo-B inhibition on PDGF-induced HBSMCs proliferation, migration and contraction were evaluated. Finally, a proteomic analysis was conducted to unveil the underlying mechanisms responsible for the function of Nogo-B.

ResultsTotal Nogo-B expression was approximately 3.08-fold lower in chronic asthmatic mice compared to naïve mice, which was obvious in the smooth muscle layer of the airways. Interference of Nogo-B expression by siRNA resulted nearly 96% reduction in mRNA in cultured HBSMCs. In addition, knockdown of Nogo-B using specific siRNA significantly decreased PDGF-induced migration of HBSMCs by 2.3-fold, and increased the cellular contraction by 16% compared to negative controls, but had limited effects on PDGF-induced proliferation. Furthermore, using proteomic analysis, we demonstrate that the expression of actin related protein 2-3 complex subunit 5 ARPC 2-3 decreased and, myosin regulatory light chain 9 isoform a MYL-9 increased after Nogo-B knockdown.

ConclusionsThese data define a novel role for Nogo-B in airway remodeling in chronic asthma. Endogenous Nogo-B, which may exert its effects through ARPC 2-3 and MYL-9, is necessary for the migration and contraction of airway smooth muscle cells.

AbbreviationsASMairway smooth muscle

Nogo-BInhibitor of neurite outgrowth-B

HBSMChuman bronchial smooth muscle cells

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-14 contains supplementary material, which is available to authorized users.

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Author: Wujian Xu - Weijun Hong - Yan Shao - Yunye Ning - Zailong Cai - Qiang Li


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