2. Academic Validation
  3. Hyaluronan delays human amniotic epithelial stem cell senescence by regulating CD44 isoform switch to activate AKT/mTOR signals

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

  • Biomed Pharmacother. 2024 Jan:170:116100. doi: 10.1016/j.biopha.2023.116100.
Chao Yu 1,  Huan Yuan 2,  Yan Xu 2,  Yi Luo 2,  Zuo-Hui Wu 3,  Jian-Jiang Zhong 4,  Jian-Hui Xiao 5
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China.
  • 2 Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China.
  • 3 Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Department of Ultrasonography, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China. Electronic address: 674645232@qq.com.
  • 4 Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. Electronic address: jjzhong@sjtu.edu.cn.
  • 5 Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Guizhou Provincial Key Laboratory of Medicinal Biotechnology & Research Center for Translational Medicine in Colleges and Universities, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China; Department of Ultrasonography, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi 563003, China. Electronic address: jianhuixiao@126.com.
PMID: 38159379 DOI: 10.1016/j.biopha.2023.116100
Abstract

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

Keywords

AKT/mTOR signaling pathway; CD44s receptor; Epithelial splicing regulatory protein 1; Hyaluronan; Stem cell senescence.

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