1. Bmi-1 determines the stemness of renal stem or progenitor cells.
- Author
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Zhou, Jiawen, Chen, Ao, Wang, Ziyang, Zhang, Jin'ge, Chen, Haiyun, Zhang, Hengzhi, Wang, Rong, Miao, Dengshun, and Jin, Jianliang
- Subjects
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PROGENITOR cells , *STEM cells , *EPITHELIAL cells , *OXIDATIVE stress , *KIDNEY failure , *PROXIMAL kidney tubules , *CELL cycle - Abstract
Renal stem or progenitor cells (RSCs), labeled with CD24 and CD133, play an important role during the repair of renal injury. Bmi-1 is a critical factor in regulating stemness of adult stem cells or progenitor cells. To investigate whether Bmi-1 determines the stemness of RSCs by inhibiting p16 and p53 , and/or maintaining redox balance, RSCs were isolated, cultured and analyzed for stemness characterizations. In RSCs from Bmi-1- deficient (Bmi-1 −/− ) mice and wild type (WT) littermates, self-renewal, stemness, and expressions of molecules for regulating redox balance and cell cycle progression were compared. Self-renewal of RSCs from Bmi-1 and p16 double-knockout (Bmi-1 −/− p16 −/− ), Bmi-1 and p53 double-knockout (Bmi-1 −/− p53 −/− ) and N-acetylcysteine (NAC)-treated Bmi-1 −/− mice were further analyzed for amelioration. Human renal proximal tubular epithelial cells (HK2) were also used for signaling analysis. Our results showed that third-passage RSCs from WT mice had good stemness; Bmi-1 deficiency led to the decreased stemness, and the increased apoptosis for RSCs; NAC treatment or p16/p53 deletion ameliorated the decreased self-renewal of RSCs in Bmi-1 deficiency mice by maintaining redox balance or inhibiting cell cycle arrest respectively; Oxidative stress (OS) could negatively feedback regulate the mRNA expressions of Bmi-1 , p16 and p53. In conclusion, Bmi-1 determined the stemness of RSCs through maintaining redox balance and preventing cell cycle arrest. Thus, Bmi-1 signaling molecules would be novel therapeutic targets for maintaining RSCs and hampering the progression of kidney diseases to prevent renal failure. • Renal stem or progenitor cells (RSCs) own good stemness and multipotency. • Bmi-1 maintains self-renewal and stemness of RSCs by inhibiting ROS, p16 and p53. • Accumulated ROS or p16 or p53 decreases self-renewal and stemness of RSCs. • NAC treatment or p16 or p53 deletion ameliorates the decreased self-renewal of RSCs. • Oxidative stress negatively feedback regulates the expression of Bmi-1 , p16 or p53. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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