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Increased IGFBP2 Levels by Placenta-Derived Mesenchymal Stem Cells Enhance Glucose Metabolism in a TAA-Injured Rat
Dae-Hyun Lee1,2, Hyeri Park1, Jun-Hyeong You1
1Department of Bioinspired Science, CHA University, Seongnam-si 13488, Republic of Korea.
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.
Insights
Placental-derived mesenchymal stem cells (PD-MSCs) improve ovarian function by enhancing glucose metabolism via the IGFBP2-AMPK pathway. This research highlights a novel therapeutic target for ovarian dysfunction.
Area of Science:
- Endocrinology
- Metabolic Research
- Stem Cell Biology
Background:
- Impaired glucose metabolism and insulin resistance are linked to ovarian dysfunction.
- The role of glucose metabolism in ovarian health requires further investigation.
Purpose of the Study:
- To investigate the effect of placental-derived mesenchymal stem cells (PD-MSCs) on ovarian glucose metabolism via the IGFBP2-AMPK signaling pathway.
- To explore the correlation between enhanced glucose metabolism and improved ovarian function.
Main Methods:
- A rat model of ovarian injury was induced using thioacetamide (TAA).
- PD-MSCs were transplanted into rats, and key gene and protein expressions (IGFBP2, AMPK, GLUT4) were analyzed.
- Ex vivo cocultivation experiments were performed to validate the effects of PD-MSCs and recombinant proteins.
Main Results:
- PD-MSC transplantation significantly increased IGFBP2, AMPK, and GLUT4 expression compared to controls.
- Follicular development markers and sex hormone levels (AMH, FSH, E2) were elevated in the PD-MSC group.
- Cocultivation confirmed that PD-MSCs and recombinant proteins upregulate IGFBP2-AMPK signaling and glucose metabolism factors.
Conclusions:
- PD-MSCs enhance ovarian glucose metabolism and function through the IGFBP2-AMPK signaling pathway.
- Increased IGFBP2 levels are crucial for mediating these beneficial effects.
- This pathway represents a potential therapeutic target for ovarian dysfunction related to metabolic disturbances.
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