Role of Wnt/β-catenin signaling activated by lithium chloride in the aging of hematopoietic stem/progenitor cell in mice

Abstract

Abstract: [Abstract] Objective To investigate the role of Wnt/β-catenin signaling activated by Lithium chloride in the aging of Sca-1 + hematopoietic stem/progenitor cell（Sca-1 + HSC/HPC）. Methods Sca-1+ HSC/HPC was isolated by magnetic cell sorting (MACS) and divided into three groups. The control group was routinely cultured; the Licl group was treated by Lithium chloride on the concentration of 10mmol/L; the aging group was added D-galactose on the concentration of 166mmol/L. All groups were cultured for 48h. The capability of colony formation was examined by CFU-Mix cultivation. The proliferation of Sca-1+ HSC/HPC was detected by CCK-8. The SA-β-Gal staining was used to investigate the aging of Sca-1+ HSC/HPC. The expression of β-catenin、GSK-3β、P53、P21 was measured by immunofluorescent staining and Western blotting. ELISA test was used to evaluate the level of 8 hydroxy deoxyguanosine (8-OH-dG). Results Compared with the control group, the proliferation of Sca-1+ HSC/HPC treated by Lithium chloride and D-galactose was blocked; the colony formation of CFU-Mix was decreased; the ratio of the SA-β-Gal staining positive Sca-1+ HSC/HPC was increased; the expression of β-catenin、P53、P21 was up-regulated and GSK-3β down-regulated ;the level of intracellular 8-OH-dG was raised. Conclusions The activation of Wnt/β-catenin signaling may lead to the aging of Sca-1+ HSC/HPC, and suggestion of Sca-1+ HSC/HPC aging may be caused by the cellular DNA oxidative damage and the up-regulation of P53/P21 pathway.

Key words: Sca-1+HSC/HPC, Lithium Chloride, Aging, Wnt/β-catenin signaling, Mechanism

Jie-Yu XIA LI jing Yan-Yan ZHANG JIA daoyong Meng-si ZHANG Lin-Bo CHEN JING pengwei Xiong-Bin CHEN Lu WANG Wang yaping. Role of Wnt/β-catenin signaling activated by lithium chloride in the aging of hematopoietic stem/progenitor cell in mice[J]. , 2016, 47(1): 34-41.

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