HAS2, or Hyaluronan Synthase 2, is a gene encoding an enzyme that generates high-molecular-weight hyaluronan (HMW-HA). Hyaluronan is a key component of the extracellular matrix, and HAS2 is involved in multiple biological processes. It is associated with pathways such as TGF-β signaling, which plays a role in processes like epithelial-mesenchymal transition (EMT) [1]. Dysregulation of HAS2 has implications for various diseases, making it an important gene for study, and genetic models can help elucidate its functions.

In a murine model of asthma, Has2 heterozygous-deficient (Has2+/-) mice showed higher sensitivity to ovalbumin (OVA), increased IL-17 release, eosinophilic infiltration, and downregulation of EIF2 signaling pathways, TGF-β signaling pathways, and heat shock proteins with Th17 bias. Has2 attenuation worsened eosinophilic airway inflammation, airway remodeling, and steroid insensitivity [3].

In another study, knocking-out HAS2 in parental estrogen receptor-positive (ER+) breast cancer cells led to anti-estrogen resistance, suggesting a role of the HAS2-Ezrin-ER axis in endocrine resistance [4].

In glioma, elevated HAS2 expression indicates poor prognosis, and it activates an antiferroptosis pathway, while its inhibition increases cellular sensitivity to ferroptosis-inducing agents [2]. Also, upregulation of HAS2 promotes glioma cell proliferation, invasion, and chemoresistance in vitro and in vivo through the c-myc pathway, and targeting HAS2 sensitizes glioma cells to chemotherapeutic agents [5].

In conclusion, HAS2 plays essential roles in processes such as airway inflammation, remodeling, and steroid sensitivity in asthma, as well as in cancer-related processes like tumor cell proliferation, chemoresistance, and endocrine resistance. The use of gene knockout mouse models in these studies has been crucial in revealing these functions, contributing to our understanding of the underlying mechanisms in these disease areas.