1. Academic Validation
  2. NANOG Attenuates Hair Follicle-Derived Mesenchymal Stem Cell Senescence by Upregulating PBX1 and Activating AKT Signaling

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

  • Oxid Med Cell Longev. 2019 Dec 4;2019:4286213. doi: 10.1155/2019/4286213.
Feilin Liu 1 2 Jiahong Shi 1 3 Yingyao Zhang 1 Aobo Lian 1 Xing Han 1 Kuiyang Zuo 1 Mingsheng Liu 1 Tong Zheng 1 Fei Zou 1 Xiaomei Liu 1 Minghua Jin 1 Ying Mu 4 Gang Li 5 Guanfang Su 2 Jinyu Liu 1
Affiliations

Affiliations

  • 1 Department of Toxicology, School of Public Health, Jilin University, Changchun, China.
  • 2 Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China.
  • 3 Department of Ultrasound, The China-Japan Union Hospital of Jilin University, Changchun, China.
  • 4 Research Center for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Laboratory of Industrial Control Technology, Zhejiang University, Hangzhou, China.
  • 5 Department of Orthopaedics & Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Abstract

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.

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