PMID- 37000316
OWN - NLM
STAT- MEDLINE
DCOM- 20230712
LR  - 20230718
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Linking)
VI  - 28
IP  - 7-8
DP  - 2023 Aug
TI  - 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.
PG  - 997-1011
LID - 10.1007/s10495-023-01833-5 [doi]
AB  - 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.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Gao, Tian
AU  - Gao T
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of 
      Chongqing Medical University, Chongqing, 400016, China. 
      gaotiandoctor@hotmail.com.
AD  - The First Affiliated Hospital of Chongqing Medical University, No.1, Yuanjiagang 
      Friendship Road, Yuzhong District, Chongqing, China. gaotiandoctor@hotmail.com.
FAU - Chen, Ying
AU  - Chen Y
AD  - Reproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China. chenying@cqmu.edu.cn.
AD  - The First Affiliated Hospital of Chongqing Medical University, No.1, Yuanjiagang 
      Friendship Road, Yuzhong District, Chongqing, China. chenying@cqmu.edu.cn.
FAU - Hu, Min
AU  - Hu M
AD  - Reproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400016, China.
FAU - Cao, Yi
AU  - Cao Y
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of 
      Chongqing Medical University, Chongqing, 400016, China.
FAU - Du, Ying
AU  - Du Y
AD  - Department of Gynecology and Obstetrics, The First Affiliated Hospital of 
      Chongqing Medical University, Chongqing, 400016, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230331
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Kruppel-Like Factor 6)
RN  - 0 (MicroRNAs)
RN  - 0 (KLF6 protein, human)
RN  - 0 (ATF3 protein, human)
RN  - 0 (Activating Transcription Factor 3)
RN  - 0 (ATF4 protein, human)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - 0 (MIRN22 microRNA, human)
SB  - IM
MH  - Female
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Primary Ovarian Insufficiency/metabolism
MH  - Cisplatin/pharmacology
MH  - *Exosomes/genetics/metabolism
MH  - Kruppel-Like Factor 6/metabolism
MH  - Apoptosis
MH  - *MicroRNAs/metabolism
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Umbilical Cord
MH  - Granulosa Cells/metabolism
MH  - Activating Transcription Factor 3/metabolism/pharmacology
MH  - Activating Transcription Factor 4/metabolism
OTO - NOTNLM
OT  - Granulosa cells
OT  - KLF6
OT  - Premature ovarian failure
OT  - hUCMSCs
OT  - miR-22-3p
EDAT- 2023/04/01 06:00
MHDA- 2023/07/12 06:42
CRDT- 2023/03/31 11:18
PHST- 2023/03/17 00:00 [accepted]
PHST- 2023/07/12 06:42 [medline]
PHST- 2023/04/01 06:00 [pubmed]
PHST- 2023/03/31 11:18 [entrez]
AID - 10.1007/s10495-023-01833-5 [pii]
AID - 10.1007/s10495-023-01833-5 [doi]
PST - ppublish
SO  - Apoptosis. 2023 Aug;28(7-8):997-1011. doi: 10.1007/s10495-023-01833-5. Epub 2023 
      Mar 31.