Pulmonary histone deacetylase is involved in phenotype transformation of airway smooth muscle cells in chronic asthmatic mice / 第二军医大学学报

ABSTRACT

Objective: To investigate the changes of histone deacetylase (HDAC) activity during chronic asthma and its effects on the phenotype and biological activities of airway smooth muscle cells. Methods: Chronic asthma model was established with mice using repeated sensitization and challenge with OVA, and the lung was homogenated for total HDAC activity assay. Rat airway smooth muscle cells and human bronchial smooth muscle cells were stimulated with trichostatin A (TSA), an HDAC inhibitor. The effect of HDAC inhibition on phenotype switching was detected by Western Blotting analysis, and its effects on proliferation, migration and contraction of smooth muscle cells were examined by MTT, Transwell and gel contraction, respectively. Results: The total HDAC activity was significantly decreased in chronic asthmatic mice compared with saline-treated controls ([0.371±0.054] vs [0.603±0.034] μmol/(L·μg), P<0.01). Incubation of the rat trachea ring and human bronchial smooth muscle cells with TSA (0.5 μmol/L) for 12-24 h increased the expression of α-sm-actin and SM22-α. TSA significantly decreased cell number after 24 h treatment ([1.719±0.044)×10 4 vs ([1.911±0.048]×104, P<0.05) and 48 h [1.808±0.009]×104 vs [2.537±0.01]×10 4, P<0.05) compared with DMSO controls. TSA treatment for 24 h also significantly decreased the migrated cells compared with the PDGF-treated cells (52±7.5 vs 88±7.632, P<0.05). Furthermore, the gel contraction rate was significantly lower in the TSA-treated cells than in the DMSO or PDGF-treated cells ([9.885±7.084]% vs [44.844±3.808]% and [41.315±7.943]%, P<0.05). Conclusion: HDAC activity is decreased in the lung of chronic asthmatic mice, which may be related to switching of the airway smooth muscle cells to a "contractic" phenotype, but with no increase of their contraction capability.