Bmi-1 determines the stemness of renal stem or progenitor cells.

Jiawen Zhou, Ao Chen, Ziyang Wang, Jin'ge Zhang, Haiyun Chen, Hengzhi Zhang, Rong Wang, Dengshun Miao, Jianliang Jin

Biochemical and biophysical research communications 2020 Sep 03

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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Jiawen Zhou, Ao Chen, Ziyang Wang, Jin'ge Zhang, Haiyun Chen, Hengzhi Zhang, Rong Wang, Dengshun Miao, Jianliang Jin. Bmi-1 determines the stemness of renal stem or progenitor cells. Biochemical and biophysical research communications. 2020 Sep 03;529(4):1165-1172