Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties

Masaki Takasugi, Denis Firsanov, Gregory Tombline, Hanbing Ning, Julia Ablaeva, Andrei Seluanov () and Vera Gorbunova ()
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Masaki Takasugi: University of Rochester
Denis Firsanov: University of Rochester
Gregory Tombline: University of Rochester
Hanbing Ning: The First Affiliated Hospital of Zhengzhou University, Zhengzhou
Julia Ablaeva: University of Rochester
Andrei Seluanov: University of Rochester
Vera Gorbunova: University of Rochester

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16050-w

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