关键词: AMPK IGFBP2 mitochondria ovarian dysfunction placenta-derived mesenchymal stem cells

Mesh : Rats Animals Thioacetamide / pharmacology AMP-Activated Protein Kinases / metabolism Mesenchymal Stem Cells / metabolism Signal Transduction Glucose / metabolism Mesenchymal Stem Cell Transplantation

来  源:   DOI:10.3390/ijms242216531   PDF(Pubmed)

Abstract:
The insulin resistance caused by impaired glucose metabolism induces ovarian dysfunction due to the central importance of glucose as a source of energy. However, the research on glucose metabolism in the ovaries is still lacking. The objectives of this study were to analyze the effect of PD-MSCs on glucose metabolism through IGFBP2-AMPK signaling and to investigate the correlation between glucose metabolism and ovarian function. Thioacetamide (TAA) was used to construct a rat injury model. PD-MSCs were transplanted into the tail vein (2 × 106) 8 weeks after the experiment started. The expression of the IGFBP2 gene and glucose metabolism factors (e.g., AMPK, GLUT4) was significantly increased in the PD-MSC group compared to the nontransplantation (NTx) group (* p < 0.05). The levels of follicular development markers and the sex hormones AMH, FSH, and E2 were also higher than those in the TAA group. Using ex vivo cocultivation, the mRNA and protein expression of IGFBP2, AMPK, and GLUT4 were significantly increased in the cocultivation with the PD-MSCs group and the recombinant protein-treated group (* p < 0.05). These findings suggest that the increased IGFBP2 levels by PD-MSCs play an important role in glucose metabolism and ovarian function through the IGFBP2-AMPK signaling pathway.
摘要:
由于葡萄糖作为能量来源的重要性,由葡萄糖代谢受损引起的胰岛素抵抗诱导卵巢功能障碍。然而,对卵巢葡萄糖代谢的研究还很缺乏。本研究的目的是分析PD-MSCs通过IGFBP2-AMPK信号传导对糖代谢的影响,并探讨糖代谢与卵巢功能的相关性。采用硫代乙酰胺(TAA)构建大鼠损伤模型。实验开始后8周,将PD-MSCs移植到尾静脉(2×106)。IGFBP2基因和葡萄糖代谢因子的表达(例如,AMPK,与非移植(NTx)组相比,PD-MSC组的GLUT4)显着增加(*p<0.05)。卵泡发育标志物和性激素AMH的水平,FSH,E2也高于TAA组。使用离体共培养,IGFBP2、AMPK、在与PD-MSCs组和重组蛋白处理组的共培养中,GLUT4显着增加(*p<0.05)。这些发现表明,PD-MSCs增加的IGFBP2水平通过IGFBP2-AMPK信号通路在糖代谢和卵巢功能中起重要作用。
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