PMID- 35271888
OWN - NLM
STAT- MEDLINE
DCOM- 20220504
LR  - 20220531
IS  - 1095-6840 (Electronic)
IS  - 0016-6480 (Linking)
VI  - 321-322
DP  - 2022 Jun 1
TI  - HucMSCs-exosomes containing miR-21 promoted estrogen production in ovarian 
      granulosa cells via LATS1-mediated phosphorylation of LOXL2 and YAP.
PG  - 114015
LID - S0016-6480(22)00040-5 [pii]
LID - 10.1016/j.ygcen.2022.114015 [doi]
AB  - BACKGROUND: Premature ovarian failure (POF) is one of the common disorders found 
      in women leading to 1% female infertility. Clinical features of POF are 
      hypoestrogenism or estrogen deficiency. With the development of regenerative 
      medicine, human mesenchymal stem cells (hMSCs) therapy brings new prospects for 
      POF. This research aims to reveal the therapeutic effects and potential 
      mechanisms of human umbilical cord mesenchymal stem cells (hucMSCs)-derived 
      exosomes on POF. METHODS: The mRNA and protein expressions in hucMSCs and ovarian 
      granulosa cells (KGN and SVOG cells) were assessed using qRT-PCR and western 
      blot. ELISA assay was performed to evaluate estradiol (E2) secretion in granulosa 
      cells. The binding relationship between miR-21 and LATS1 was verified by 
      dual-luciferase reporter assay and RNA binding protein immunoprecipitation assay 
      (RIP) assay. Additionally, Immunoprecipitation assay was carried out to confirm 
      Lysyl oxidase like 2 (LOXL2) was phosphorylated by large tumor suppressor 1 
      (LATS1). Finally, the binding relationships between Yes-associated protein (YAP), 
      StAR and LOXL2 were verified by dual-luciferase reporter assay and/or chromatin 
      immunoprecipitation assay (ChIP) assay. RESULTS: Here our results displayed that 
      miR-21 was overexpressed in hucMSCs and hucMSCs-derived exosomes, compared with 
      that ovarian granulosa cells. hucMSC-exo with overexpressing miR-21 could 
      markedly promote the secretion of estrogen in ovarian granulosa cells. LATS1 
      overexpression in ovarian granulosa cells reduced the secretion of estrogen. We 
      subsequently confirmed that LATS1 was the target of miR-21. In addition, LATS1 
      could regulate StAR expression by phosphorylating LOXL2 and YAP. CONCLUSION: 
      miR-21 carried by hucMSCs-derived exosomes could downregulate LATS1, thereby 
      reducing phosphorylated LOXL2 and YAP, and ultimately promoting estrogen 
      secretion in ovarian granulosa cells.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Cai, Jun-Hong
AU  - Cai JH
AD  - Central Laboratory, Hainan General Hospital/Hainan Affiliated Hospital of Hainan 
      Medical University, Haikou, Hainan Province 570311, People's Republic of China.
FAU - Sun, Yu-Ting
AU  - Sun YT
AD  - Hainan Medical University, Haikou, Hainan Province 571199, People's Republic of 
      China.
FAU - Bao, Shan
AU  - Bao S
AD  - Department of Gynaecology and Obstetrics, Hainan Affiliated Hospital of Hainan 
      Medical University/Hainan General Hospital, Haikou, Hainan Province 570311, 
      People's Republic of China. Electronic address: baoshan3@hainmc.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220307
PL  - United States
TA  - Gen Comp Endocrinol
JT  - General and comparative endocrinology
JID - 0370735
RN  - 0 (Estrogens)
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 1.4.- (Amino Acid Oxidoreductases)
RN  - EC 1.4.3.- (LOXL2 protein, human)
RN  - EC 2.7.1.- (LATS1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acid Oxidoreductases/metabolism
MH  - Estrogens/metabolism
MH  - *Exosomes/genetics/metabolism
MH  - Female
MH  - Granulosa Cells/metabolism
MH  - Humans
MH  - Male
MH  - *Mesenchymal Stem Cells/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/genetics
MH  - Umbilical Cord/metabolism
OTO - NOTNLM
OT  - Exosome
OT  - LATS1
OT  - POF
OT  - YAP
OT  - hucMSC
OT  - miR-21
EDAT- 2022/03/11 06:00
MHDA- 2022/05/06 06:00
CRDT- 2022/03/10 20:12
PHST- 2021/12/13 00:00 [received]
PHST- 2022/02/23 00:00 [revised]
PHST- 2022/03/03 00:00 [accepted]
PHST- 2022/03/11 06:00 [pubmed]
PHST- 2022/05/06 06:00 [medline]
PHST- 2022/03/10 20:12 [entrez]
AID - S0016-6480(22)00040-5 [pii]
AID - 10.1016/j.ygcen.2022.114015 [doi]
PST - ppublish
SO  - Gen Comp Endocrinol. 2022 Jun 1;321-322:114015. doi: 10.1016/j.ygcen.2022.114015. 
      Epub 2022 Mar 7.