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Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
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The aim of this study is to investigate whether vitamin D3 supplementation in CRF rats could improve the function of kidney and hippocampus by increasing the number and activity of circulating endothelial progenitor cells (EPCs) and to explore the related mechanism, so as to provide a new theoretical basis for clinical application.
1. In vitro part: the co-culture system of mouse hippocampal neurons and human-derived circulating EPCs was established by Transwell chamber, which was divided into 4 groups: Ctrl group, EPC-MN-h group (normal human circulating EPCs plus mouse hippocampal neurons), CRF-EPC-MN-H group (CRF patient circulating EPCs plus EPC-MN-h), and CRF-EPC-MN-h+L-NAME. The activity of hippocampal neurons and the expression of SYT-3, MAP-2, eNOS and BDNF were detected separately.
2. In vivo part: (1) Kidney part: experimental animals were randomly divided into 4 groups: Ctrl_8w group, CKD_8w group, CKD_8w+calcitriol group. The number and the ability of circulating EPCs, renal function, pathological changes and CD31+ were detected. (2) Hippocampus: The mice were divided into 3 groups: Ctrl_8w group, CKD_8w group, CKD_8w+calcitriol group. The changes in the neuroelectrophysiology of hippocampal neurons and the corresponding markers were detected.
1.In vitro:The viability of hippocampal neurons was significantly enhanced after co-culture with normal circulating EPCs (p<0.05 vs Ctrl). But the activity of hippocampal neurons in the CRF-EPC-MN-h group was decreased (p <0.0001 vs EPC-MN-h), and further decreased after the intervention with eNOS inhibitor L-NAME (p <0.01). The EPC-MN-h group significantly increased in the expressions of eNOS, BDNF, SYT-3 and MAP-2 (p <0.05 vs Ctrl), while the expressions in the CRF-EPC-MN-h group were significantly lower (p <0.05 vs EPC-MN-h).These expressions were further decreased by L-NAME(p <0.05). The changes of SYT-3 and MAP-2 expression were consistent with the results of WB.
2.In vivo: (1) Kidney: The calcitriol group had more circulating EPCs, adherent cells and formed more lumen-like structures (p=0.0097, 0.0019,0.0019 vs CKD_8w). The renal injury score of CKD_8w+calcitriol group was significantly lower (p<0.01 vs CKD_8w). Calcitriol supplementation significantly increased the expression of CD31(p=0.0034). (2) In hippocampus: Calcitriol significantly enhanced mEPSC and the amplitude of AMPAR-EPSC and NMDAR-EPSC in model group (p <0.05, vs CKD_8w group).The protein expressions of SYT-3 and MAP2 of model group were significantly increased after calcitriol intervention.
Circulating EPCs may improve the activity of hippocampal neurons through the eNOS-BDNF pathway and regulate the expression of synaptic key proteins SYT-3 and MAP2 that affect the release of neurotransmitters, thereby affecting the transmission of signal transmitters between hippocampal neurons.
The intervention of active vitamin D3 can promote the number and function of circulating EPCs, thereby improving the synaptic plasticity of hippocampal neurons and promoting the expression of SYT-3 and MAP2.
Therefore, we believe that the decrease and function of circulating EPCs is an important cause of hippocampal neuronal dysfunction in chronic renal failure, and active vitamin D3 may play a protective role in hippocampus and kidney by promoting the increase in the number of circulating EPCs.
