摘要
Background An important physiological feature of asthma is the phenotypic change of airway smooth muscle cells （ASMCs）, but the precise mechanisms behind the ASMCs＇ change remains unknown. Our study assessed whether p21Ras can directly modulate the phenotype of ASMCs. Methods Rat ASMCs were treated with FTP Ill, a highly specific p21Ras inhibitor. ASMCs were identified via immunocytochemistry. The ultrastructure of cells was observed by electron microscopy, and the expression of a-actin was evaluated by Western blotting analysis. The levels of IL-6 and RANTES were measured by enzyme linked immunosorbent assay （ELISA）. Results It was observed that ASMCs in asthma exhibited a proliferative/secretory phenotype and were larger, denser and had many pseudopods, as well as increased signs of secretory organelles. Additionally, the level of a-actin, a marker of ASMCs, was reduced in asthmatic ASMCs and the secretion of ~L-6 and RANTES was increased. When FTP Ⅲ was added to asthmatic ASMCs it induced a contractile phenotype, with increased a-actin levels and reduced secretion of IL-6 and RANTES. Conclusions It appears that p21Ras induces asthmatic ASMCs to a proliferative/secretory phenotype, but its inhibitor FTP Ⅲ, can significantly reverse this phenotype. The role of p21Ras in the ASMCs may be a new target for asthma treatment.
Background An important physiological feature of asthma is the phenotypic change of airway smooth muscle cells （ASMCs）, but the precise mechanisms behind the ASMCs＇ change remains unknown. Our study assessed whether p21Ras can directly modulate the phenotype of ASMCs. Methods Rat ASMCs were treated with FTP Ill, a highly specific p21Ras inhibitor. ASMCs were identified via immunocytochemistry. The ultrastructure of cells was observed by electron microscopy, and the expression of a-actin was evaluated by Western blotting analysis. The levels of IL-6 and RANTES were measured by enzyme linked immunosorbent assay （ELISA）. Results It was observed that ASMCs in asthma exhibited a proliferative/secretory phenotype and were larger, denser and had many pseudopods, as well as increased signs of secretory organelles. Additionally, the level of a-actin, a marker of ASMCs, was reduced in asthmatic ASMCs and the secretion of ~L-6 and RANTES was increased. When FTP Ⅲ was added to asthmatic ASMCs it induced a contractile phenotype, with increased a-actin levels and reduced secretion of IL-6 and RANTES. Conclusions It appears that p21Ras induces asthmatic ASMCs to a proliferative/secretory phenotype, but its inhibitor FTP Ⅲ, can significantly reverse this phenotype. The role of p21Ras in the ASMCs may be a new target for asthma treatment.
