Fig. 5: Schematic model of the mechanism of protective effect of vHMM-HA.
From: Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties
Our data indicate that vHMM-HA attenuates CD44 protein-protein interactions (PPI), whereas HMM-HA promotes them. Concomitantly, vHMM-HA suppresses CD44-dependent gene expression, including those regulated by CD44-dependent transcription factors such as ELK, EGR1, and CD44-ICD. vHMM-HA and HMM-HA thereby induce opposing effects on the expression of CD44-dependent genes, which are also associated with the p53 pathway. As a result, vHMM-HA partially attenuates p53 and its target genes, and protects cells in a p53-dependent manner.
