HAS1

Hyaluronan synthase 1 (HAS1) is a transmembrane enzyme responsible for synthesizing hyaluronic acid (HA), a key component of the extracellular matrix. Also termed HA synthase 1, it catalyzes the alternating addition of UDP-N-acetylglucosamine and UDP-glucuronic acid to form HA polymers, which regulate tissue hydration, cell adhesion, and inflammation. HAS1 activity is modulated through PI3K/Akt and MAPK signaling pathways, influencing processes like wound healing and tumor progression. Dysregulation of HAS1 has been implicated in fibrotic disorders, osteoarthritis, and cancers, where aberrant HA accumulation promotes metastasis or immune evasion.
Elevated HAS1 expression correlates with poor prognosis in breast and ovarian cancers, while its suppression ameliorates fibrosis in preclinical models. Current therapeutic strategies targeting HAS1 include small-molecule inhibitors (e.g., 4-Methylumbelliferone) to block HA synthesis and monoclonal antibodies disrupting HA-CD44 interactions. Notably, HAS1-specific antisense oligonucleotides are under evaluation for fibrotic lung diseases. Despite challenges in isoform-specific targeting, HAS1 remains a promising candidate for modulating HA-driven pathologies, with several compounds advancing to Phase II clinical trials for oncology and inflammatory conditions.