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hUMSC 移植通过 AMPK/mTOR 信号通路抑制颗粒细胞-间质细胞自噬来恢复 POI 大鼠的卵巢功能。

hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway.

机构信息

College of Basic Medicine & Institute of Reproductive Diseases, Binzhou Medical University, Yantai, 264003, Shandong, China.

College of Basic Medicine, Binzhou Medical University, Yantai, 264003, Shandong, China.

出版信息

Stem Cell Res Ther. 2020 Jul 3;11(1):268. doi: 10.1186/s13287-020-01784-7.

DOI:10.1186/s13287-020-01784-7
PMID:32620136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7333437/
Abstract

BACKGROUND

Previous studies of primary ovarian insufficiency (POI) have focused on granulosa cells (GCs) and ignored the role of theca-interstitial cells (TICs). This study aims to explore the mechanism of the protective effects of human umbilical cord-derived mesenchymal stem cells (hUMSCs) on ovarian function in POI rats by regulating autophagy of TICs.

METHODS

The POI model was established in rats treated with cisplatin (CDDP). The hUMSCs were transplanted into POI rats by tail vein. Enzyme-linked immunosorbent assay (ELISA) analysis, hematoxylin and eosin (HE) staining, and immunohistochemistry were used to measure the protective effects of hUMSCs. The molecular mechanisms of injury and repairment of TICs were assessed by immunofluorescence, transmission electron microscope (TEM), flow cytometry (FCM), western blot, and quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

In vivo, hUMSC transplantation restored the ovarian function and alleviated the apoptosis of TICs in POI rats. In vitro, hUMSCs reduced the autophagy levels of TICs by reducing oxidative stress and regulating AMPK/mTOR signaling pathway, thereby alleviating the apoptosis of TICs.

CONCLUSION

This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

摘要

背景

先前关于原发性卵巢功能不全 (POI) 的研究主要集中在颗粒细胞 (GCs) 上,而忽略了卵丘间质细胞 (TICs) 的作用。本研究旨在通过调节 TIC 自噬来探讨人脐带间充质干细胞 (hUMSC) 对 POI 大鼠卵巢功能的保护作用机制。

方法

采用顺铂 (CDDP) 处理建立 POI 大鼠模型。通过尾静脉将 hUMSC 移植到 POI 大鼠中。采用酶联免疫吸附试验 (ELISA) 分析、苏木精和伊红 (HE) 染色和免疫组织化学检测 hUMSC 的保护作用。通过免疫荧光、透射电子显微镜 (TEM)、流式细胞术 (FCM)、Western blot 和实时定量聚合酶链反应 (qRT-PCR) 评估 TIC 损伤和修复的分子机制。

结果

体内,hUMSC 移植恢复了 POI 大鼠的卵巢功能并减轻了 TIC 的凋亡。体外,hUMSCs 通过减少氧化应激和调节 AMPK/mTOR 信号通路降低了 TIC 的自噬水平,从而减轻了 TIC 的凋亡。

结论

本研究表明,hUMSC 通过调节 AMPK/mTOR 自噬信号通路保护 POI 中的卵巢功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02eb/7333437/16250caa2069/13287_2020_1784_Fig7_HTML.jpg
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