Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Hyaluronan (HA) is essentially secreted by every cell and plays a critical role in maintaining normal cell physiology. While the structure and function of HA have been extensively investigated, questions regarding the sizes and conformation of HA under physiological and inflamed conditions, in relevance to its functions, remain elusive. In this article, we update our knowledge of the HA functional properties, including binding proteins and their signaling networks, as well as matrix formation, which can potentially induce phase separation and affect the mobility and behavior of small molecules, proteins, and cells. We detail the striking differences regarding the biological outcomes of signaling pathways for HA and membrane receptors versus HA and GPI-linked hyaluronidase Hyal-2. We describe: (1) the native, large-sized HA is not proapoptotic but signals with an overexpressed HYAL-2/WWOX/SMAD4 complex to induce apoptosis, which is likely to occur in an inflamed microenvironment; (2) HA-binding proteins are connected via signal pathway networks. The competitive binding of HA and TGF-β to the membrane HYAL-2 and the downstream HYAL-2/WWOX/SMAD4 signaling is addressed; (3) the phase-separated proteins or small molecules in the HA matrices may contribute to the aberrant interactions, leading to inflammation and disease progression; (4) the role of HA and complement C1q in Alzheimer

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.