PMID- 36241227
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20221102
IS  - 1671-167X (Print)
IS  - 1671-167X (Linking)
VI  - 54
IP  - 5
DP  - 2022 Oct 18
TI  - [Kindlin-2 regulates endometrium development via mTOR and Hippo signaling 
      pathways in mice].
PG  - 846-852
AB  - OBJECTIVE: To investigate the effects and mechanisms of Kindlin-2 on uterus 
      development and reproductive capacity in female mice. METHODS: Cdh16-Cre tool 
      mice and Kindlin-2(flox/flox) mice were used to construct the mouse model of 
      uterus specific knockout of Kindlin-2, and the effects of Kindlin-2 deletion on 
      uterine development and reproduction capacity of female mice were observed. High 
      expression and knockdown of Kindlin-2 in endometrial cancer cell lines HEC-1 and 
      Ish were used to detect the regulation of mammalian target of rapamycin (mTOR) 
      signaling pathway. In addition, uterine proteins of the female mice with specific 
      knockout of Kindlin-2 and female mice in the control group were extracted to 
      detect the protein levels of key molecules of mTOR signaling pathway and Hippo 
      signaling pathway. RESULTS: The mouse model of uterine specific knockout of 
      Kindlin-2 was successfully constructed. The knockout efficiency of Kindlin-2 in 
      mouse uterus was identified and verified by mouse tail polymerase chain reaction 
      (PCR), Western blot protein identification, immunohistochemical staining (IHC) 
      and other methods. Compared with the control group, the female mice with uterus 
      specific deletion of Kindlin-2 lost weight, seriously impaired reproductive 
      ability, and the number of newborn mice decreased, but the proportion of the 
      female mice and male mice in the newborn mice did not change. Hematoxylin eosin 
      staining (HE) experiment showed that the endometrium of Kindlin-2 knockout group 
      was incomplete and the thickness of uterine wall became thinner. In terms of 
      mechanism, the deletion of Kindlin-2 in endo-metrial cancer cell lines HEC-1 and 
      Ish could downregulate the protein levels of mTOR, phosphorylated mTOR, adenosine 
      monophosphate-activated protein kinase (AMPK), phosphorylated AMPK and 
      phosphorylated ribosomal protein S6 (S6), and the mTOR signal pathway was 
      inhibited. It was found that the specific deletion of Kindlin-2 could upregulate 
      the protein levels of Mps one binding 1 (MOB1) and phosphorylated Yes-associated 
      protein (YAP) in the uterus of the female mice, and the Hippo signal pathway was 
      activated. CONCLUSION: Kindlin-2 inhibits the development of uterus by inhibiting 
      mTOR signal pathway and activating Hippo signal pathway, thereby inhibiting the 
      fertility of female mice.
FAU - Zhang, J
AU  - Zhang J
AD  - Department of Human Anatomy, Histology and Embryology, Peking University School 
      of Basic Medical Sciences, Beijing 100191, China.
FAU - Song, J G
AU  - Song JG
AD  - Department of Human Anatomy, Histology and Embryology, Peking University School 
      of Basic Medical Sciences, Beijing 100191, China.
AD  - Center of Basic Medical Research, Institute of Medical Innovation and Research, 
      Cancer Center, Peking University Third Hospital, Beijing 100191, China.
FAU - Wang, Z B
AU  - Wang ZB
AD  - Department of Human Anatomy, Histology and Embryology, Peking University School 
      of Basic Medical Sciences, Beijing 100191, China.
FAU - Gong, Y Q
AU  - Gong YQ
AD  - Department of Human Anatomy, Histology and Embryology, Peking University School 
      of Basic Medical Sciences, Beijing 100191, China.
FAU - Wang, T Z
AU  - Wang TZ
AD  - Department of Human Anatomy, Histology and Embryology, Peking University School 
      of Basic Medical Sciences, Beijing 100191, China.
FAU - Zhou, J Y
AU  - Zhou JY
AD  - Department of Human Anatomy, Histology and Embryology, Peking University School 
      of Basic Medical Sciences, Beijing 100191, China.
FAU - Zhan, J
AU  - Zhan J
AD  - Department of Human Anatomy, Histology and Embryology, Peking University School 
      of Basic Medical Sciences, Beijing 100191, China.
FAU - Zhang, H Q
AU  - Zhang HQ
AD  - Department of Human Anatomy, Histology and Embryology, Peking University School 
      of Basic Medical Sciences, Beijing 100191, China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Beijing Da Xue Xue Bao Yi Xue Ban
JT  - Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health 
      sciences
JID - 101125284
RN  - 0 (Cadherins)
RN  - 0 (Cdh16 protein, mouse)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (kindlin-2 protein, mouse)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - TDQ283MPCW (Eosine Yellowish-(YS))
RN  - W36ZG6FT64 (Sirolimus)
RN  - YKM8PY2Z55 (Hematoxylin)
SB  - IM
MH  - *AMP-Activated Protein Kinases/metabolism
MH  - Adenosine Monophosphate/metabolism
MH  - Animals
MH  - Cadherins/metabolism
MH  - Cytoskeletal Proteins/metabolism
MH  - Endometrium/metabolism
MH  - Eosine Yellowish-(YS)/metabolism
MH  - Female
MH  - Hematoxylin/metabolism
MH  - *Hippo Signaling Pathway
MH  - Male
MH  - Mammals/metabolism
MH  - Mice
MH  - Muscle Proteins
MH  - Ribosomal Protein S6/metabolism
MH  - Sirolimus/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - YAP-Signaling Proteins
PMC - PMC9568384
OTO - NOTNLM
OT  - Endometrium
OT  - Hippo signaling pathway
OT  - Kindlin-2
OT  - Mouse model, specific knockout
OT  - mTOR signaling pathway
EDAT- 2022/10/15 06:00
MHDA- 2022/10/19 06:00
PMCR- 2022/10/18
CRDT- 2022/10/14 20:53
PHST- 2022/10/14 20:53 [entrez]
PHST- 2022/10/15 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/10/18 00:00 [pmc-release]
AID - bjdxxbyxb-54-5-846 [pii]
AID - 10.19723/j.issn.1671-167X.2022.05.012 [doi]
PST - ppublish
SO  - Beijing Da Xue Xue Bao Yi Xue Ban. 2022 Oct 18;54(5):846-852. doi: 
      10.19723/j.issn.1671-167X.2022.05.012.