Abstract
Asthma has been proven to be a respiratory disorder that is characterized by the airway remodeling, airway inflammation and reversible airway obstruction. The 1,25-hydroxyvitamin D3 (1,25-(OH)2D3) plays critical roles in delaying remodeling. To investigate the effects of 1,25-(OH)2D3 on the airway remodeling in tumor necrosis factor α (TNF-α)-induced airway smooth muscle cells (ASMCs). The human ASMCs were divided into a blank control group (without treatment), a TNF-α group (treated with 10 ng/mL TNF-α) and a 1,25-(OH)2D3+TNF-α group (pre-treated with 10-7 M 1,25-(OH)2D3, then with 10 ng/mL TNF-α). The MTT assay was used to evaluate cell proliferation. Matrix Gla protein (MGP) and transforming growth factor β1 (TGF-β1) were examined using western blot assay. The TNF-α treatment significantly increased ASMCs proliferation and enhanced MGP and TGF-β1 expression compared to a blank control group (p < 0.05). The 1,25-(OH)2D3 treatment (1,25-(OH)2D3+TNF-α group) significantly inhibited cell viability (0.83 ±0.01), compared to that in the TNF-α group (0.92 ±0.01) (p < 0.05). The 1,25-(OH)2D3 treatment significantly downregulated MGP expression (0.61 ±0.02), compared to that of the TNF-α group (1.51 ±0.35) (p < 0.05). The 1,25-(OH)2D3 treatment significantly reduced TGF-β1 expression (0.69 ±0.17), compared to that of the TNF-α group (1.6 ±0.18) (p < 0.05). The 1,25-(OH)2D3 could participate and modulate airway remodeling by reducing MGP and TGF-β1 expression in TNF-α-induced ASMCs. This study provided therapeutic insight and theoretical basis for clinical research.
Highlights
Asthma has been proven to be a respiratory disorder that is characterized by the airway remodeling, airway inflammation and reversible airway obstruction
The tumor necrosis factor α (TNF-α) treatment significantly increased airway smooth muscle cells (ASMCs) proliferation and enhanced Matrix Gla protein (MGP) and transforming growth factor β1 (TGF-β1) expression compared to a blank control group (p < 0.05)
In this study, we evaluated the expression of MGP and TGF-β1 in TNF-α-stimulated ASMCs to verify the effects of 1,25-(OH)2D3 on the airway remodeling
Summary
Asthma has been proven to be a respiratory disorder that is characterized by the airway remodeling, airway inflammation and reversible airway obstruction. The 1,25-hydroxyvitamin D3 (1,25-(OH)2D3) plays critical roles in delaying remodeling. The ASMCs could synthesize and release the cytokines and inflammatory factors, and accelerate the airway remodeling in the asthma processes.[5] The tumor necrosis factor α (TNF-α), a kind of pro-inflammatory cytokine, could induce the formation of synthetic ASMCs.[6] in this study, the TNF-α was administered to ASMCs to establish a synthetic ASMCs model of asthma
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