PMID- 26438838
OWN - NLM
STAT- MEDLINE
DCOM- 20160209
LR  - 20181113
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 112
IP  - 42
DP  - 2015 Oct 20
TI  - Epithelial estrogen receptor 1 intrinsically mediates squamous differentiation in 
      the mouse vagina.
PG  - 12986-91
LID - 10.1073/pnas.1513550112 [doi]
AB  - Estrogen-mediated actions in female reproductive organs are tightly regulated, 
      mainly through estrogen receptor 1 (ESR1). The mouse vaginal epithelium 
      cyclically exhibits cell proliferation and differentiation in response to 
      estrogen and provides a unique model for analyzing the homeostasis of stratified 
      squamous epithelia. To address the role of ESR1-mediated tissue events during 
      homeostasis, we analyzed mice with a vaginal epithelium-specific knockout of Esr1 
      driven by keratin 5-Cre (K5-Esr1KO). We show here that loss of epithelial ESR1 in 
      the vagina resulted in aberrant epithelial cell proliferation in the suprabasal 
      cell layers and led to failure of keratinized differentiation. Gene expression 
      analysis showed that several known estrogen target genes, including erbB growth 
      factor ligands, were not induced by estrogen in the K5-Esr1KO mouse vagina. Organ 
      culture experiments revealed that the addition of erbB growth factor ligands, 
      such as amphiregulin, could activate keratinized differentiation in the absence 
      of epithelial ESR1. Thus, epithelial ESR1 integrates estrogen and growth factor 
      signaling to mediate regulation of cell proliferation in squamous 
      differentiation, and our results provide new insights into estrogen-mediated 
      homeostasis in female reproductive organs.
FAU - Miyagawa, Shinichi
AU  - Miyagawa S
AD  - Okazaki Institute for Integrative Bioscience, National Institute for Basic 
      Biology, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan; 
      Department of Basic Biology, Faculty of Life Science, SOKENDAI (The Graduate 
      University for Advanced Studies), Okazaki, Aichi 444-8787, Japan.
FAU - Iguchi, Taisen
AU  - Iguchi T
AD  - Okazaki Institute for Integrative Bioscience, National Institute for Basic 
      Biology, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan; 
      Department of Basic Biology, Faculty of Life Science, SOKENDAI (The Graduate 
      University for Advanced Studies), Okazaki, Aichi 444-8787, Japan 
      taisen@nibb.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151005
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Estrogen Receptor alpha)
SB  - IM
MH  - Animals
MH  - Cell Death/physiology
MH  - Cell Differentiation/*physiology
MH  - Cell Proliferation/physiology
MH  - Epithelium/metabolism
MH  - Estrogen Receptor alpha/genetics/*physiology
MH  - Female
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Vagina/*pathology
PMC - PMC4620905
OTO - NOTNLM
OT  - amphiregulin
OT  - epithelium
OT  - estrogen receptor
OT  - keratinization
OT  - vagina
COIS- The authors declare no conflict of interest.
EDAT- 2015/10/07 06:00
MHDA- 2016/02/10 06:00
PMCR- 2016/04/20
CRDT- 2015/10/07 06:00
PHST- 2015/10/07 06:00 [entrez]
PHST- 2015/10/07 06:00 [pubmed]
PHST- 2016/02/10 06:00 [medline]
PHST- 2016/04/20 00:00 [pmc-release]
AID - 1513550112 [pii]
AID - 201513550 [pii]
AID - 10.1073/pnas.1513550112 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):12986-91. doi: 
      10.1073/pnas.1513550112. Epub 2015 Oct 5.