High molecular weight hyaluronan attenuates fine particulate matter induced acute lung injury through inhibition of ROS-ASK1-p38/JNK-mediated epithelial apoptosis

Inhalation of fine particulate matter (PM2.5) is asscoiated with lung injury. High molecular weight hyaluronan (HMW-HA) is an essential constituent of extracellular matrix (ECM), exhibiting anti-oxidative and anti-inflammatory properties when administered by injection, inhalation, nebulization or gene delivery of HA synthases. The aim of the present study is to determine whether HMW-HA alleviates PM2.5-induced acute lung injury (ALI) and investigate the underlying mechanisms. We observed that HMW-HA suppressed pathological injury, inflammation, oxidative stress, edema and epithelial damage caused by PM2,5 in the lungs of the rats. The protective mechanism of HMW-HA was further explored in vitro. The results elucidated that reactive oxygen species (ROS) was involved in PM2.5-induced cell apoptosis, and HMW-HA mitigated the oxidative potential of PM2.5, subsequently inhibiting phosphorylation of ASK1 at Thr845, downstream phosphorylation of p38 and JNK, and eventual apoptosis. Our study indicates that HMW-HA is a promising strategy in the prevention of PM2.5-induced pulmonary damage.