Effect of p21Ras in vitro intervention on the phenotype of airway smooth muscle cells from asthmatic rats / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>Rat ASMCs were treated with FTP III, a highly specific p21Ras inhibitor. ASMCs were identified via immunocytochemistry. The ultrastructure of cells was observed by electron microscopy, and the expression of α-actin was evaluated by Western blotting analysis. The levels of IL-6 and RANTES were measured by enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>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 α-actin, a marker of ASMCs, was reduced in asthmatic ASMCs and the secretion of IL-6 and RANTES was increased. When FTP III was added to asthmatic ASMCs it induced a contractile phenotype, with increased α-actin levels and reduced secretion of IL-6 and RANTES.</p><p><b>CONCLUSIONS</b>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.</p>