Hyaluronan delays human amniotic epithelial stem cell senescence by regulating CD44 isoform switch to activate AKT/mTOR signals

• DOI: 10.1016/j.biopha.2023.116100
• Publication Date: 2023-12-29T17:53:31Z
• Authors: Chao Yu; Huan Yuan; Yan Xu; Yi Luo; Zuo-Hui Wu; Jian-Jiang Zhong; Jian-Hui Xiao
• Keywords: Senescence; LY294002

The replicative senescence of human amniotic epithelial stem cells (hAECs) is a major concern towards its clinical application. This study found that 300-kDa hyaluronic acid (HA) could effectively delay the hAECs, as indicated by downregulation cellular markers and alteration cell cycle, substantially improve differentiation capacities hAECs. HA was confirmed to regulate CD44 isoform switch upregulating CD44s downregulating CD44v, thus exerting an anti-aging effect. We further induced upregulation hyaluronan synthase (HAS) 2, resulting in activation splicing regulatory protein 1 (ESRP1) alternative mRNA, thereby promoting expression inhibiting CD44v expression. Knockdown HAS2 blocked ESRP1 attenuated effects HA. Hermes-1, specific blocker CD44, caused partial loss effect HA, upregulated markers, downregulated stemness markers. Furthermore, receptor shown initiate AKT/mTOR downstream signaling. Conclusively, suggested delayed hAEC regulating activate signaling pathway, there potential for application hAECs combination with