PMID- 31262977
OWN - NLM
STAT- MEDLINE
DCOM- 20200818
LR  - 20211204
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 7
DP  - 2019 Jul 31
TI  - EPHA3 enhances macrophage autophagy and apoptosis by disrupting the mTOR 
      signaling pathway in mice with endometriosis.
LID - BSR20182274 [pii]
LID - 10.1042/BSR20182274 [doi]
AB  - Background: Endometriosis is a chronic fibrotic disease characterized by 
      agonizing pelvic pain and low fertility, mainly affecting middle-aged women. The 
      aim of the present study is to assess the potential effects of 
      erythropoietin-producing hepatocellular carcinoma A3 (EPHA3) on endometriosis, 
      with emphasis on the autophagy and apoptosis of macrophages via inhibition of the 
      mammalian target of rapamycin (mTOR) signaling pathway.Methods: The mouse models 
      of endometriosis were established followed by culturing the macrophages and 
      macrophage transfection via the EPHA3 vector, siRNA EPHA3, and RAPA (an inhibitor 
      of the mTOR signaling pathway). The expression of EPHA3, related factors in the 
      mTOR signaling pathway, macrophage autophagy (autophagy-related gene 3 (Atg3), 
      light chain 3-I (LC3-I), light chain 3-II (LC3-II) and Beclin1) and apoptosis 
      (B-cell lymphoma-2 (bcl-2), bax and fas) were all detected and documented, 
      respectively. The changes of autophagic lysosomes and the apoptosis of 
      macrophages in each group following transfection were also inspected and 
      detected.Results: The results of the in silico analysis ascertained EPHA3 to be a 
      candidate gene of endometriosis. After successful modeling, the uterine tissues 
      of endometriosis mice presented with a low expression of EPHA3 and activated mTOR 
      signaling pathway. Overexpression of EPHA3 inhibited the activation of the mTOR 
      signaling pathway, down-regulated bcl-2 expression, up-regulated the expression 
      of Atg3, LC3-II/LC3-I, Beclin1, bax and fas, and also promoted the autophagy and 
      apoptosis of macrophages in endometriosis mice.Conclusion: Altogether, EPHA3 
      could potentially promote the autophagy and apoptosis of macrophages in 
      endometriosis via inhibition of the mTOR signaling pathway, highlighting the 
      potential of EPHA3 as the target to treat endometriosis.
CI  - (c) 2019 The Author(s).
FAU - Xu, Hongmei
AU  - Xu H
AD  - Department of Obstetrics, The First Hospital of Jilin University, Changchun 
      130021, Jilin, China.
FAU - Gao, Yongmei
AU  - Gao Y
AD  - Department of Obstetrics, The First Hospital of Jilin University, Changchun 
      130021, Jilin, China.
FAU - Shu, Yang
AU  - Shu Y
AD  - Department of Gynaecology and Obstetrics, The First Hospital of Jilin University, 
      Changchun 130021, Jilin, China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Department of Gynaecology and Obstetrics, The First Hospital of Jilin University, 
      Changchun 130021, Jilin, China.
FAU - Shi, Qingyang
AU  - Shi Q
AUID- ORCID: 0000-0002-4877-8925
AD  - Centre for Reproductive Medicine, Centre for Prenatal Diagnosis, The First 
      Hospital of Jilin University, Changchun 130021, Jilin, China 
      shiqingyang1111@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190730
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.10.1 (Epha3 protein, mouse)
RN  - EC 2.7.10.1 (Receptor, EphA3)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - *Autophagic Cell Death
MH  - Disease Models, Animal
MH  - Endometriosis/genetics/*metabolism/pathology
MH  - Female
MH  - Macrophages/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Receptor, EphA3/genetics/*metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC6667729
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - EPHA3
OT  - Endometriosis
OT  - Macrophage
OT  - mTOR signaling pathway
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/07/03 06:00
MHDA- 2020/08/19 06:00
PMCR- 2019/07/30
CRDT- 2019/07/03 06:00
PHST- 2018/12/06 00:00 [received]
PHST- 2019/05/27 00:00 [revised]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/07/03 06:00 [pubmed]
PHST- 2020/08/19 06:00 [medline]
PHST- 2019/07/03 06:00 [entrez]
PHST- 2019/07/30 00:00 [pmc-release]
AID - BSR20182274 [pii]
AID - 10.1042/BSR20182274 [doi]
PST - epublish
SO  - Biosci Rep. 2019 Jul 30;39(7):BSR20182274. doi: 10.1042/BSR20182274. Print 2019 
      Jul 31.