Regulates the Development of Ovalbumin-Induced Airway Remodeling and Steroid Insensitivity in Mice.

is a member of the gene family encoding the hyaluronan synthase 2, which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified as a candidate gene for increased susceptibility to adult asthma. However, whether dysfunction affects airway remodeling and steroid insensitivity is still limited. Therefore, this study aimed to clarify the dysfunction, triggering severe airway remodeling and steroid insensitivity in a murine model of asthma. heterozygous-deficient () mice and their wild-type littermates have been evaluated in a model of chronic ovalbumin (OVA) sensitization and challenge. Mice present a higher sensitivity to OVA and higher IL-17 release as well as eosinophilic infiltration. RNA sequencing demonstrated the downregulation of EIF2 signaling pathways, TGF-β signaling pathways, and heat shock proteins with Th17 bias in -OVA mice. The combined treatment with anti-IL-17A antibody and dexamethasone reduces steroid insensitivity in -OVA mice. attenuation worsens eosinophilic airway inflammation, airway remodeling, and steroid insensitivity. These data highlight that HAS2 and HMW-HA are important for controlling intractable eosinophilic airway inflammation and remodeling and could potentially be exploited for their therapeutic benefits in patients with asthma.