MicroRNA-22-3p in human umbilical cord mesenchymal stem cell-secreted exosomes inhibits granulosa cell apoptosis by targeting KLF6 and ATF4-ATF3-CHOP pathway in POF mice

作者全名："Gao, Tian; Chen, Ying; Hu, Min; Cao, Yi; Du, Ying"

作者地址："[Gao, Tian; Cao, Yi; Du, Ying] Chongqing Med Univ, Dept Gynecol & Obstet, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Chen, Ying; Hu, Min] Chongqing Med Univ, Reprod Med Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Gao, Tian; Chen, Ying] Chongqing Med Univ, Affiliated Hosp 1, 1 Yuanjiagang Friendship Rd, Chongqing, Peoples R China"

通信作者："Gao, T (通讯作者)，Chongqing Med Univ, Dept Gynecol & Obstet, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Chen, Y (通讯作者)，Chongqing Med Univ, Reprod Med Ctr, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Gao, T; Chen, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Yuanjiagang Friendship Rd, Chongqing, Peoples R China."

来源：APOPTOSIS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000961234500001

JCR分区：Q2

影响因子：7.2

年份：2023

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期号：　

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文献类型：Article; Early Access

关键词：Premature ovarian failure; miR-22-3p; hUCMSCs; Granulosa cells; KLF6

摘要："Background: Human umbilical cord mesenchymal stem cells (hUCMSCs)-derived exosomes carrying microRNAs (miRNAs) have promising therapeutic potential in various disorders, including premature ovarian failure (POF). Previous evidence has revealed the low plasma level of miR-22-3p in POF patients. Nevertheless, exosomal miR-22-3p specific functions underlying POF progression are unclarified. Methods: A cisplatin induced POF mouse model and in vitro murine ovarian granulosa cell (mOGC) model were established. Exosomes derived from miR-22-3p-overexpressed hUCMSCs (Exos-miR-22-3p) were isolated. CCK-8 assay and flow cytometry were utilized for measuring mOGC cell viability and apoptosis. RT-qPCR and western blotting were utilized for determining RNA and protein levels. The binding ability between exosomal miR-22-3p and Kruppel-like factor 6 (KLF6) was verified using luciferase reporter assay. Hematoxylin-eosin staining, ELISA, and TUNEL staining were performed for examining the alteration of ovarian function in POF mice. Results: Exos-miR-22-3p enhanced mOGC viability and attenuated mOGC apoptosis under cisplatin treatment. miR-22-3p targeted KLF6 in mOGCs. Overexpressing KLF6 reversed the above effects of Exos-miR-22-3p. Exos-miR-22-3p ameliorated cisplatin-triggered ovarian injury in POF mice. Exos-miR-22-3p repressed ATF4-ATF3-CHOP pathway in POF mice and cisplatin-treated mOGCs. Conclusion: Exosomal miR-22-3p from hUCMSCs alleviates OGC apoptosis and improves ovarian function in POF mouse models by targeting KLF6 and ATF4-ATF3-CHOP pathway."

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