Abstract
BackgroundAirway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs). S100A8 is a calcium-binding protein with a potential to regulate cell proliferation. Here, the effect of exogenous S100A8 protein on the proliferation of ASMCs induced by platelet-derived growth factor (PDGF) and the underlying molecular mechanism was investigated.MethodsRat ASMCs were cultured with or without a neutralizing antibody to the receptor for advanced glycation end-products (RAGE), a potential receptor for S100A8 protein. Purified recombinant rat S100A8 protein was then added into the cultured cells, and the proliferation of ASMCs induced by PDGF was detected by colorimetric-based WST-8 assay and ampedance-based xCELLigence proliferation assay. The expression levels of RAGE in ASMCs were analyzed using western blotting assay.ResultsResults showed that exogenous S100A8 inhibited the PDGF-induced proliferation of rat ASMCs in a dose-dependent manner with the maximal effect at 1 μg/ml in vitro. Furthermore, when ASMCs was pre-treated with anti-RAGE neutralizing antibody, the inhibitory effect of S100A8 on PDGF-induced proliferation was significantly suppressed. In addition, neither the treatment with S100A8 or PDGF alone nor the pre-treatment with rS100A8 followed by PDGF stimulation affected the expression levels of RAGE.ConclusionsOur study demonstrated that S100A8 inhibits PDGF-induced ASMCs proliferation in a manner dependent on membrane receptor RAGE.
Highlights
Airway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs)
RS100A8 inhibits the platelet-derived growth factor (PDGF)‐induced proliferation of ASMCs The effect of different doses of rat S100A8 protein (rS100A8) (50 ng/ml, 100 ng/ml, 250 ng/ml, 500 ng/ml, 1 μg/ml, 2.5 μg/ml and 5 μg/ml) on PDGF-induced ASMC proliferation was Protein extraction and western blotting Cells were harvested after the treatment with PDGF and/ or S100A8 protein, and the membrane protein fraction was isolated using Transmembrane Protein Extraction Kit (Novagen, Madison, WI) according to the manufacturer’s instructions
We showed that exogenous S100A8 protein significantly inhibited PDGF-BB induced ASMCs proliferation via the membrane receptor receptor for advanced glycation end-products (RAGE)
Summary
Airway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs). S100A8 is a calcium-binding protein with a potential to regulate cell proliferation. The effect of exogenous S100A8 protein on the proliferation of ASMCs induced by platelet-derived growth factor (PDGF) and the underlying molecular mechanism was investigated. Airway remodeling is a hallmark pathological feature of chronic inflammatory airway diseases including asthma, chronic obstructive pulmonary disease and other types of bronchiectasis. It is often considered the result of longstanding airway inflammation and leads to narrowing of the bronchial lumen and progressive loss of. The protective mechanisms that prevent or attenuate the growth factor-induced proliferation of ASMCs are feasible therapeutic targets for the treatment of inflammatory airway diseases. The effects and mechanisms of S100A8 on ASMCs proliferation remain unclear
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