Document Detail

CTGF expression is up-regulated by PROK1 in early pregnancy and influences HTR-8/Svneo cell adhesion and network formation.
MedLine Citation:
PMID:  21098624     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Prokineticin-1 (PROK1) and connective tissue growth factor (CTGF) are expressed in human endometrium and first-trimester decidua and have individually been proposed to have roles in implantation and placentation. We have recently demonstrated that CTGF may be a target gene for PROK1 in gene array analysis of a prokineticin receptor-1 stably transfected Ishikawa endometrial epithelial cell line (PROKR1-Ishikawa). The first aim of the study was to determine the effect of PROK1 on CTGF expression in PROKR1-Ishikawa cells and first-trimester decidua samples. Secondly, the effect of CTGF on trophoblast-derived HTR-8/SVneo cell adhesion and network formation was investigated.
METHODS AND RESULTS: Real-time qPCR showed that CTGF expression is elevated in first-trimester decidua compared with non-pregnant endometrium. In decidua, CTGF co-localized with PROKR1 to the glandular epithelium and a subset of stromal cells. PROK1 increased CTGF mRNA and protein expression in PROKR1-Ishikawa cells and first-trimester human decidua (8-12 weeks gestation). Knock down of endogenous PROK1 using micro RNA constructs targeted at PROK1, resulted in decreased expression of CTGF mRNA and protein in decidua. Inhibitors of specific cell signalling molecules demonstrated that PROK1 regulates CTGF expression via the Gq, phospholipase C (PLC), cSrc, epidermal growth factor receptor (EGFR), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) kinase pathway activation. Treatment of trophoblast-derived HTR-8/Svneo cells with 1 µg/ml CTGF significantly increased adhesion to collagen IV, and differentiation of the cells into tube-like structures in matrigel.
CONCLUSIONS: CTGF expression in early pregnancy decidua is regulated by PROK1, via activation of the Gq, PLC, cSrc, EGFR, MAPK/ERK kinase pathway. CTGF in turn may contribute to the regulation of trophoblast conversion of maternal spiral arteries.
Jennifer M Waddell; Jemma Evans; Henry N Jabbour; Fiona C Denison
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-23
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  26     ISSN:  1460-2350     ISO Abbreviation:  Hum. Reprod.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-23     Completed Date:  2011-04-26     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  67-75     Citation Subset:  IM    
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MeSH Terms
Cell Adhesion*
Cell Line
Connective Tissue Growth Factor / genetics*,  metabolism,  physiology
Decidua / metabolism
Embryo Implantation / genetics
Extracellular Matrix / metabolism
Gastrointestinal Hormones / genetics,  physiology*
Pregnancy Trimester, First / genetics*,  metabolism,  physiology
Receptor, Serotonin, 5-HT1B / physiology*
Signal Transduction
Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / genetics,  physiology*
Grant Support
G1002033//Medical Research Council; //Medical Research Council
Reg. No./Substance:
0/CTGF protein, human; 0/Gastrointestinal Hormones; 0/HTR1B protein, human; 0/PROK1 protein, human; 0/Receptor, Serotonin, 5-HT1B; 0/Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; 139568-91-5/Connective Tissue Growth Factor

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