4-乙烯基环己烯二氧化物通过调节 miR-144 诱导颗粒细胞自噬，从而导致大鼠卵巢早衰。
4-vinylcyclohexene diepoxide induces premature ovarian insufficiency in rats by triggering the autophagy of granule cells through regulating miR-144.
机构信息
Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, China.
Department of Massage, The First Affiliated Hospital of Zhejiang Chinese Medical University, China.
出版信息
J Reprod Immunol. 2023 Jun;157:103928. doi: 10.1016/j.jri.2023.103928. Epub 2023 Mar 5.
This research explored the pathological and molecular mechanisms of 4-vinylcyclohexene diepoxide (VCD)-induced POI model. QRT-PCR was exploited to detect miR-144 expression in the peripheral blood of POI patients. Rat and KGN cells were treated with VCD to construct POI rat or cell model, respectively. After miR-144 agomir or MK-2206 treatment, miR-144 level, follicle damage, autophagy level and expressions of key pathway-related proteins in rats were detected, and cell viability and autophagy in KGN cells were detected. MiR-144 was apparently down-regulated in the peripheral blood of POI patients. Decreased miR-144 was viewed in both the serum and ovary of rats, yet this trend was apparently reversed by miR-144 agomir. The increased concentration of Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH), along with decreased concentration of E2 and AMH, was observed in the serum of model rats, which was conspicuously negated by control agomir or miR-144 agomir. Increased number of autophagosomes, up-regulated PTEN, and inactivated AKT/m-TOR pathway induced by VCD in ovary tissues were strikingly offset by miR-144 agomir. Results of cytotoxicity assay revealed that 2 mM VCD prominently repressed KGN cell viability. In vitro experiments confirmed that miR-144 interfered with the effect of VCD on autophagy in KGN cells through the AKT/mTOR pathway. Taken together, VCD triggers autophagy to induce POI after targeting the AKT pathway by inhibiting miR-144, it suggest that up-regulation the expression of miR-144 may have the potential to treat POI.
本研究旨在探讨 4-乙烯基环己烯二氧化物（VCD）诱导 POI 模型的病理和分子机制。利用 QRT-PCR 检测 POI 患者外周血中 miR-144 的表达。用 VCD 处理大鼠和 KGN 细胞，分别构建 POI 大鼠或细胞模型。用 miR-144 agomir 或 MK-2206 处理后，检测大鼠 miR-144 水平、卵泡损伤、自噬水平及关键通路相关蛋白表达情况，检测 KGN 细胞活力和自噬情况。POI 患者外周血中 miR-144 明显下调。大鼠血清和卵巢中 miR-144 均减少，但 miR-144 agomir 可明显逆转这种趋势。模型大鼠血清中促卵泡激素（FSH）和黄体生成素（LH）浓度升高，雌二醇（E2）和抗苗勒管激素（AMH）浓度降低，而对照 agomir 或 miR-144 agomir 则明显否定了这一趋势。VCD 诱导卵巢组织中自噬小体数量增加、PTEN 上调、AKT/m-TOR 通路失活，而 miR-144 agomir 则明显逆转了这一趋势。细胞毒性检测结果表明，2 mM VCD 明显抑制 KGN 细胞活力。体外实验证实，miR-144 通过 AKT/mTOR 通路干扰 VCD 对 KGN 细胞自噬的影响。综上所述，VCD 通过抑制 miR-144 靶向 AKT 通路诱导自噬，从而引发 POI，提示上调 miR-144 的表达可能具有治疗 POI 的潜力。
Zotero 插件