Yang Lina, Wu Lan, Du Shuyan, Hu Ye, Fan Yi, Ma Jianfei
Department of Nephrology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, P.R. China.
Mol Med Rep. 2016 Jul;14(1):839-44. doi: 10.3892/mmr.2016.5323. Epub 2016 May 23.
The regulation of cell proliferation, differentiation and immunomodulation are affected by 1,25(OH)2D3. However, its function during apoptosis and oxidative stress in human peritoneal mesothelial cells (HPMCs) remains unknown. The aim of the present study was to investigate whether the regulation of apoptosis and oxidative stress have therapeutic relevance in peritoneal dialysis (PD) therapy. The present study investigated the effects of 1,25(OH)2D3 on high glucose (HG)-induced apoptosis and reactive oxygen species (ROS) production in HPMCs, and examined the underlying molecular mechanisms. Flow cytometry and western blotting were performed to detect cell apoptosis, 2,7-dichlorofluorescein diacetate was used to measure reactive oxygen species production and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to measure cell viability. The results of the present study demonstrated that exposure to HG increased apoptosis and ROS production in HPMCs, whereas pretreatment with 1,25(OH)2D3 significantly inhibited HG‑induced apoptosis and ROS production. Further analysis revealed that 1,25(OH)2D3 facilitated cell survival via the MAPK/P38 pathway. The results of the present study indicate that 1,25(OH)2D3 inhibits apoptosis and ROS production in HG‑induced HPMCs via inhibition of the MAPK/P38 pathway.
细胞增殖、分化及免疫调节受1,25(OH)2D3的影响。然而，其在人腹膜间皮细胞（HPMCs）凋亡及氧化应激过程中的作用仍不清楚。本研究的目的是探究凋亡和氧化应激的调节在腹膜透析（PD）治疗中是否具有治疗意义。本研究调查了1,25(OH)2D3对高糖（HG）诱导的HPMCs凋亡及活性氧（ROS）生成的影响，并检测了潜在的分子机制。采用流式细胞术和蛋白质免疫印迹法检测细胞凋亡，用二氯荧光素二乙酸酯检测活性氧生成，用噻唑蓝检测细胞活力。本研究结果表明，暴露于HG会增加HPMCs的凋亡及ROS生成，而用1,25(OH)2D3预处理可显著抑制HG诱导的凋亡及ROS生成。进一步分析显示，1,25(OH)2D3通过丝裂原活化蛋白激酶/ P38通路促进细胞存活。本研究结果表明，1,25(OH)2D3通过抑制丝裂原活化蛋白激酶/ P38通路抑制HG诱导的HPMCs凋亡及ROS生成。
