051 Superoxide Regulates α‐SMA via p‐38 MAPK

Abstract

This study was to investigate the effect of cyclic mechanical stretching on superoxide and nitric oxide production in human patellar tendon fibroblasts (HPTFs) and to establish the role of superoxide and p38 MAPK in stretching‐induced α‐smooth muscle actin (α‐SMA) expression. When HPTFs were grown in deformable silicone dishes and subjected to 8% cyclic, uniaxial stretching, it was found that HPTFs markedly increased the production of superoxide and nitrite but not nitric oxide. And, cyclic stretching of HPTFs increased phosphorylation of p38 MAPK with increasing stretching magnitude. In addition, stretching duration also influenced the expression of phosphorylated p38 MAPK, where the dependence followed a pattern of cellular response in p38 MAPK activation consistent with previous studies using human mesangial cells and rat 3Y1 fibroblasts. For short stretching durations (∼15 min), the expression of phosphorylated p38 MAPK increased rapidly but decreased for longer stretching durations. Furthermore, in HPTFs treated with superoxide dismutase (SOD), which converts superoxide anions to hydrogen peroxide and an oxygen molecule, levels of stretching‐induced p38 MAPK phosphorylation and α‐SMA expression decreased compared to stretched fibroblasts not treated with SOD. Similarly, cells treated with SB202190, which specifically inhibits p38 MAPK activation, also decreased α‐SMA expression levels. Therefore, these results suggest that superoxide regulates stretching‐induced α‐SMA expression via p38 MAPK activation in HPTFs subjected to cyclic stretching conditions.