Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32398747.
- Also identified by DOI 10.1038/s41467-020-16050-w and PMC identifier 7217962.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Naked mole-rat (NMR), the longest-living rodent, produces very-high-molecular-mass hyaluronan (vHMM-HA), compared to other mammalian species. However, it is unclear if exceptional polymer length of vHMM-HA is important for longevity. Here, we show that vHMM-HA (>6.1 MDa) has superior cytoprotective properties compared to the shorter HMM-HA. It protects not only NMR cells, but also mouse and human cells from stress-induced cell-cycle arrest and cell death in a polymer length-dependent manner. The cytoprotective effect is dependent on the major HA-receptor, CD44. We find that vHMM-HA suppresses CD44 protein-protein interactions, whereas HMM-HA promotes them. As a result, vHMM-HA and HMM-HA induce opposing effects on the expression of CD44-dependent genes, which are associated with the p53 pathway. Concomitantly, vHMM-HA partially attenuates p53 and protects cells from stress in a p53-dependent manner. Our results implicate vHMM-HA in anti-aging mechanisms and suggest the potential applications of vHMM-HA for enhancing cellular stress resistance.
Medical subject headings
- Cytoprotection
- Gene Expression Regulation
- Hyaluronan Receptors
- Hyaluronic Acid