PMID- 29025069
OWN - NLM
STAT- MEDLINE
DCOM- 20180625
LR  - 20181113
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 97
IP  - 3
DP  - 2017 Sep 1
TI  - WNK lysine deficient protein kinase 1 regulates human endometrial stromal cell 
      decidualization, proliferation, and migration in part through mitogen-activated 
      protein kinase 7.
PG  - 400-412
LID - 10.1093/biolre/iox108 [doi]
AB  - The differentiation of endometrial stromal cells into decidual cells, termed 
      decidualization, is an integral step in the establishment of pregnancy. The 
      mitogen-activated protein kinase homolog, WNK lysine deficient protein kinase 1 
      (WNK1), is activated downstream of epidermal growth factor receptor during 
      decidualization. Primary human endometrial stromal cells (HESCs) were subjected 
      to small interfering RNA knockdown of WNK1 followed by in vitro decidualization. 
      This abrogated expression of the decidual marker genes, insulin like growth 
      factor binding protein 1 (IGFBP1) and prolactin (PRL), and prevented adoption of 
      decidual cell morphology. Analysis of the WNK1-dependent transcriptome by RNA-Seq 
      demonstrated that WNK1 regulates the expression of 1858 genes during 
      decidualization. Gene ontology and upstream regulator pathway analysis showed 
      that WNK1 regulates cell migration, differentiation, and proliferation. WNK1 was 
      required for many of the gene expression changes that drive decidualization, 
      including the induction of the inflammatory cytokines, C-C motif chemokine ligand 
      8 (CCL8), interleukin 1 beta (IL1B), and interleukin 15 (IL15), and the 
      repression of transforming growth factor-beta (TGF-beta) pathway genes, including 
      early growth response 2 (EGR2), SMAD family member 3 (SMAD3), integrin subunit 
      alpha 2 (ITGA2), integrin subunit alpha 4 (ITGA4), and integrin subunit beta 3 
      (ITGB3). In addition to abrogating decidualization, WNK1 knockdown decreased the 
      migration and proliferation of HESCs. Furthermore, mitogen-activated protein 
      kinase 7 (MAPK7), a known downstream target of WNK1, was activated during 
      decidualization in a WNK1-dependent manner. Small interfering RNA knockdown of 
      MAPK7 demonstrated that MAPK7 regulates a subset of WNK1-regulated genes and 
      controls the migration and proliferation of HESCs. These results indicate that 
      WNK1 and MAPK7 promote migration and proliferation during decidualization and 
      regulate the expression of inflammatory cytokines and TGF-beta pathway genes in 
      HESCs.
CI  - Published by Oxford University Press on behalf of Society for the Study of 
      Reproduction 2017.
FAU - Adams, Nyssa R
AU  - Adams NR
AD  - Reproductive and Developmental Biology Laboratory, National Institute of 
      Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
AD  - Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor 
      College of Medicine, Houston, Texas, USA.
FAU - Vasquez, Yasmin M
AU  - Vasquez YM
AD  - Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
FAU - Mo, Qianxing
AU  - Mo Q
AD  - Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
FAU - Gibbons, William
AU  - Gibbons W
AD  - Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, 
      Texas, USA.
FAU - Kovanci, Ertug
AU  - Kovanci E
AD  - Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, 
      Texas, USA.
FAU - DeMayo, Francesco J
AU  - DeMayo FJ
AD  - Reproductive and Developmental Biology Laboratory, National Institute of 
      Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Cytokines)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.1 (WNK Lysine-Deficient Protein Kinase 1)
RN  - EC 2.7.11.1 (WNK1 protein, human)
RN  - EC 2.7.11.24 (MAPK7 protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7)
SB  - IM
MH  - Adult
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cytokines/biosynthesis/genetics
MH  - Decidua/*cytology
MH  - Endometrium/*cytology
MH  - Female
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Mitogen-Activated Protein Kinase 7/*genetics/*physiology
MH  - RNA, Small Interfering/pharmacology
MH  - Stromal Cells/*physiology
MH  - Transforming Growth Factor beta/biosynthesis/genetics
MH  - WNK Lysine-Deficient Protein Kinase 1/*deficiency/*genetics
PMC - PMC6109229
OTO - NOTNLM
OT  - cell culture
OT  - cytokines
OT  - endometrium
OT  - extracellular matrix
OT  - kinases
OT  - signal transduction
EDAT- 2017/10/13 06:00
MHDA- 2018/06/26 06:00
PMCR- 2018/09/01
CRDT- 2017/10/13 06:00
PHST- 2017/07/14 00:00 [received]
PHST- 2017/08/28 00:00 [accepted]
PHST- 2017/10/13 06:00 [pubmed]
PHST- 2018/06/26 06:00 [medline]
PHST- 2017/10/13 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - 4097577 [pii]
AID - iox108 [pii]
AID - 10.1093/biolre/iox108 [doi]
PST - ppublish
SO  - Biol Reprod. 2017 Sep 1;97(3):400-412. doi: 10.1093/biolre/iox108.