NANOG Attenuates Hair Follicle-Derived Mesenchymal Stem Cell Senescence by Upregulating PBX1 and Activating AKT Signaling

Autor: Jin Yu Liu, Kuiyang Zuo, Fei Zou, Tong Zheng, Feilin Liu, Xing Han, Minghua Jin, Mingsheng Liu, Ying Mu, Aobo Lian, Guanfang Su, Xiaomei Liu, Jiahong Shi, Yingyao Zhang, Gang Li
Rok vydání: 2019
Předmět:
Cyclin-Dependent Kinase Inhibitor p21
Homeobox protein NANOG
Aging
Article Subject
Morpholines
Poly (ADP-Ribose) Polymerase-1
Apoptosis
Biochemistry
Downregulation and upregulation
medicine
Humans
lcsh:QH573-671
Promoter Regions
Genetic
Protein Kinase Inhibitors
Protein kinase B
Cells
Cultured
Cellular Senescence
Cyclin-Dependent Kinase Inhibitor p16
PI3K/AKT/mTOR pathway
Cell Proliferation
Gene knockdown
lcsh:Cytology
Chemistry
Cell Cycle
Pre-B-Cell Leukemia Transcription Factor 1
Mesenchymal stem cell
Mesenchymal Stem Cells
Nanog Homeobox Protein
Cell Biology
General Medicine
Hair follicle
Up-Regulation
Cell biology
Enzyme Activation
HEK293 Cells
medicine.anatomical_structure
Chromones
Tumor Suppressor Protein p53
Stem cell
Hair Follicle
Proto-Oncogene Proteins c-akt
Signal Transduction
Research Article
Zdroj: Oxidative Medicine and Cellular Longevity
Oxidative Medicine and Cellular Longevity, Vol 2019 (2019)
ISSN: 1942-0994
1942-0900
Popis: Stem cells derived from elderly donors or harvested by repeated subculture exhibit a marked decrease in proliferative capacity and multipotency, which not only compromises their therapeutic potential but also raises safety concerns for regenerative medicine. NANOG—a well-known core transcription factor—plays an important role in maintaining the self-renewal and pluripotency of stem cells. Unfortunately, the mechanism that NANOG delays mesenchymal stem cell (MSC) senescence is not well-known until now. In our study, we showed that both ectopic NANOG expression and PBX1 overexpression (i) significantly upregulated phosphorylated AKT (p-AKT) and PARP1; (ii) promoted cell proliferation, cell cycle progression, and osteogenesis; (iii) reduced the number of senescence-associated-β-galactosidase- (SA-β-gal-) positive cells; and (iv) downregulated the expression of p16, p53, and p21. Western blotting and dual-luciferase activity assays showed that ectopic NANOG expression significantly upregulated PBX1 expression and increased PBX1 promoter activity. In contrast, PBX1 knockdown by RNA interference in hair follicle- (HF-) derived MSCs that were ectopically expressing NANOG resulted in the significant downregulation of p-AKT and the upregulation of p16 and p21. Moreover, blocking AKT with the PI3K/AKT inhibitor LY294002 or knocking down AKT via RNA interference significantly decreased PBX1 expression, while increasing p16 and p21 expression and the number of SA-β-gal-positive cells. In conclusion, our findings show that NANOG delays HF-MSC senescence by upregulating PBX1 and activating AKT signaling and that a feedback loop likely exists between PBX1 and AKT signaling.
Databáze: OpenAIRE
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