PMID- 20610537
OWN - NLM
STAT- MEDLINE
DCOM- 20101222
LR  - 20211020
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 24
IP  - 9
DP  - 2010 Sep
TI  - Targeted disruption of Mapk14 (p38MAPKalpha) in granulosa cells and cumulus cells 
      causes cell-specific changes in gene expression profiles that rescue COC 
      expansion and maintain fertility.
PG  - 1794-804
LID - 10.1210/me.2010-0086 [doi]
AB  - MAPK14 (p38MAPKalpha) is critical for FSH and prostaglandin E (PGE)2 signaling 
      cascades in granulosa cells (GCs) and cumulus cell-oocyte complexes (COCs) in 
      culture, indicating that this kinase might impact follicular development and COC 
      expansion in vivo. Because Mapk14 knockout mice are embryonic lethal, we 
      generated GC specific Mapk14 knockout mice (Mapk14gc(-/-)) by mating 
      Mapk14(fl/fl) and Cyp19-Cre mice. Unexpectedly, the Mapk14gc(-/-) female mice 
      were fertile. Analyses of gene expression patterns showed that amphiregulin 
      (Areg) and epiregulin (Ereg), two key regulators of ovulation and COC expansion, 
      were up-regulated in the GCs but down-regulated in cumulus cells of the mutant 
      mice in vivo. COCs from the mutant mice expanded and expressed matrix-related 
      genes, if cultured with AREG, but not when cultured with forskolin or PGE2, the 
      latter being a key factor regulating MAPK14 activity in cumulus cells. 
      Conversely, when GCs from the Mapk14gc(-/-) mice were cultured with forskolin, 
      they produced more Areg and Ereg mRNA than did wild-type GCs. These results 
      indicate that disruption of Mapk14 selectively alters the expression of Areg and 
      other genes in each cell type. Greater AREG and EREG produced by the GCs appears 
      to by-pass and compensate for the critical need for MAPK14 signaling and 
      induction of Areg/Ereg (and hence matrix genes) by PGE2 in cumulus cells of the 
      mutant mice. In conclusion, although MAPK14 is not overtly essential for 
      preovulatory follicle development or events associated with ovulation and 
      luteinization in vivo, it does impact gene expression profiles.
FAU - Liu, Zhilin
AU  - Liu Z
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, TX 77030, USA.
FAU - Fan, Heng-Yu
AU  - Fan HY
FAU - Wang, Yibin
AU  - Wang Y
FAU - Richards, Joanne S
AU  - Richards JS
LA  - eng
GR  - U54-HD-007495/HD/NICHD NIH HHS/United States
GR  - R56 HD016229/HD/NICHD NIH HHS/United States
GR  - HD-16229/HD/NICHD NIH HHS/United States
GR  - U54 HD007495/HD/NICHD NIH HHS/United States
GR  - R37 HD016229/HD/NICHD NIH HHS/United States
GR  - R01 HD016229/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100707
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 1F7A44V6OU (Colforsin)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Colforsin/pharmacology
MH  - Cumulus Cells/cytology/drug effects/*enzymology
MH  - Dinoprostone/pharmacology
MH  - EGF Family of Proteins
MH  - Female
MH  - Fertility/drug effects/*genetics
MH  - Follicle Stimulating Hormone/pharmacology
MH  - *Gene Deletion
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation/drug effects
MH  - *Gene Targeting
MH  - Glycoproteins/pharmacology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/pharmacology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 14/antagonists & inhibitors/*genetics
MH  - Oocytes/*cytology/drug effects/enzymology
MH  - Organ Specificity/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Transport/drug effects
MH  - Signal Transduction/drug effects
PMC - PMC2940481
EDAT- 2010/07/09 06:00
MHDA- 2010/12/24 06:00
PMCR- 2011/09/01
CRDT- 2010/07/09 06:00
PHST- 2010/07/09 06:00 [entrez]
PHST- 2010/07/09 06:00 [pubmed]
PHST- 2010/12/24 06:00 [medline]
PHST- 2011/09/01 00:00 [pmc-release]
AID - me.2010-0086 [pii]
AID - 4698 [pii]
AID - 10.1210/me.2010-0086 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2010 Sep;24(9):1794-804. doi: 10.1210/me.2010-0086. Epub 2010 Jul 
      7.