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  3. Hypoxia improves self-renew and migration of urine-derived stem cells by upregulating autophagy and mitochondrial function through ERK signal pathway

Hypoxia improves self-renew and migration of urine-derived stem cells by upregulating autophagy and mitochondrial function through ERK signal pathway

  • Mitochondrion. 2023 Sep 9;73:1-9. doi: 10.1016/j.mito.2023.09.001.
Chaoqun Hu 1,  Yanting Sun 2,  Wanxia Li 3,  Yang Bi 4
Affiliations

Affiliations

  • 1 Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, The Children's Hospital of Chongqing Medical University, Chongqing, China; Digestive Department, Chongqing People's Hospital, Chongqing, China.
  • 2 Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, The Children's Hospital of Chongqing Medical University, Chongqing, China; Centre of Clinical Laboratory, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
  • 3 Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, The Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, The Children's Hospital of Chongqing Medical University, Chongqing, China. Electronic address: yang_bi@hospital.cqmu.edu.cn.
PMID: 37678426 DOI: 10.1016/j.mito.2023.09.001
Abstract

Urine-derived stem cells (USCs) are autologous stem cells with self-renewal ability and multi-lineage differentiation potential. Our previous studies have shown that hypoxia preconditioning can improve self-renewal and migration abilities of USCs by up-regulating Autophagy. The purpose of this study was to investigate the specific mechanism by which hypoxia treatment promotes the biological function of USCs. We found that hypoxia treatment upregulated the expression of phosphralated ERK protein without affecting the expression of total ERK protein. Inhibiting ERK signaling with the PD98059 inhibitor decreased cell proliferation, migration and colony formation during hypoxia treatment. Hypoxia increased ATP production, mitochondrial membrane potential and mt-DNA copy number, which were reversed by inhibiting the ERK signal. Additionally, the number of autophagosomes and autophagic lysosomes was significantly lower in PD98059 group than in the hypoxia group. PD98059 treatment inhibited the up-regulation of Autophagy related proteins induced by hypoxia. Therefore, this study suggests that hypoxia improves the self-renewal and migration abilities of USCs by upregulating Autophagy and mitochondrial function through ERK signaling pathway. This finding may provide a new therapeutic mechanism for hypoxia pretreated USCs as a source of stem cell transplantation.

Keywords

Autophagy; ERK signal pathway; Hypoxia; Mitochondrial function; Urine-derived stem cells.

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