GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-26 (MMP-26), one of the main mediators of extracellular matrix (ECM) degradation, has been shown to exist in trophoblasts of human placenta and to play a role in trophoblast cell invasion. However, little is...

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Main Authors: Wu Xiao-qiu, Li Yu-xia, Cao Bin, Liu Jing, Wang Yan-ling
Format: Article
Language:English
Published: BMC 2010-01-01
Series:Reproductive Biology and Endocrinology
Online Access:http://www.rbej.com/content/8/1/5
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author Wu Xiao-qiu
Li Yu-xia
Cao Bin
Liu Jing
Wang Yan-ling
author_facet Wu Xiao-qiu
Li Yu-xia
Cao Bin
Liu Jing
Wang Yan-ling
author_sort Wu Xiao-qiu
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-26 (MMP-26), one of the main mediators of extracellular matrix (ECM) degradation, has been shown to exist in trophoblasts of human placenta and to play a role in trophoblast cell invasion. However, little is known about the regulation of MMP-26 expression in human trophoblasts. Recently, gonadotropin-releasing hormone I (GnRH I) and GnRH II have been shown to regulate the expression of MMP-2, MMP-9/tissue inhibitor of metalloproteinases 1 (TIMP-1), and urokinase plasminogen activator (uPA)/plasminogen activator inhibitor (PAI) in human trophoblasts, suggesting that these two hormones may work as paracrine and/or autocrine regulators in modulating the activities of various protease systems at the feto-maternal interface. In this study, we determined the regulatory effects of GnRH I and GnRH II on the expression of MMP-26 in human immortalized cytotrophoblast-like cell line, B6Tert-1.</p> <p>Methods</p> <p>Real-time PCR was used to quantify mRNA levels of MMP-26 in human trophoblast-like cell line, B6Tert-1 and primary cultured cytotrophoblasts. Western blotting was used to characterize the expression of MMP-26 and the phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) in B6Tert-1 cells after treatment with GnRH I and GnRH II.</p> <p>Results</p> <p>We found that GnRH I increased MMP-26 expression in B6Tert-1 cells after 12 h of treatment at both the mRNA and protein level, while GnRH II increased MMP-26 expression beginning at 3 h of treatment. Treatment of GnRH I at 1 nM resulted in maximal increase of MMP-26 mRNA and protein levels, whereas GnRH II treatment at a concentration of 100 nM was required to induce maximal increase in MMP-26 expression. In addition, we demonstrated that the activation of JNK, but not ERK1/2, was required for GnRH I and II-stimulated MMP-26 production in B6Tert-1 cells and primary cytotrophoblasts.</p> <p>Conclusions</p> <p>These novel findings indicated that GnRH I and II could up-regulate MMP-26 expression through the JNK signaling pathway in human trophoblast-like/trophoblast cells.</p>
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spelling doaj.art-6ac721e67634438298b69e905fa7fac52022-12-21T20:47:24ZengBMCReproductive Biology and Endocrinology1477-78272010-01-0181510.1186/1477-7827-8-5GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblastsWu Xiao-qiuLi Yu-xiaCao BinLiu JingWang Yan-ling<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-26 (MMP-26), one of the main mediators of extracellular matrix (ECM) degradation, has been shown to exist in trophoblasts of human placenta and to play a role in trophoblast cell invasion. However, little is known about the regulation of MMP-26 expression in human trophoblasts. Recently, gonadotropin-releasing hormone I (GnRH I) and GnRH II have been shown to regulate the expression of MMP-2, MMP-9/tissue inhibitor of metalloproteinases 1 (TIMP-1), and urokinase plasminogen activator (uPA)/plasminogen activator inhibitor (PAI) in human trophoblasts, suggesting that these two hormones may work as paracrine and/or autocrine regulators in modulating the activities of various protease systems at the feto-maternal interface. In this study, we determined the regulatory effects of GnRH I and GnRH II on the expression of MMP-26 in human immortalized cytotrophoblast-like cell line, B6Tert-1.</p> <p>Methods</p> <p>Real-time PCR was used to quantify mRNA levels of MMP-26 in human trophoblast-like cell line, B6Tert-1 and primary cultured cytotrophoblasts. Western blotting was used to characterize the expression of MMP-26 and the phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) in B6Tert-1 cells after treatment with GnRH I and GnRH II.</p> <p>Results</p> <p>We found that GnRH I increased MMP-26 expression in B6Tert-1 cells after 12 h of treatment at both the mRNA and protein level, while GnRH II increased MMP-26 expression beginning at 3 h of treatment. Treatment of GnRH I at 1 nM resulted in maximal increase of MMP-26 mRNA and protein levels, whereas GnRH II treatment at a concentration of 100 nM was required to induce maximal increase in MMP-26 expression. In addition, we demonstrated that the activation of JNK, but not ERK1/2, was required for GnRH I and II-stimulated MMP-26 production in B6Tert-1 cells and primary cytotrophoblasts.</p> <p>Conclusions</p> <p>These novel findings indicated that GnRH I and II could up-regulate MMP-26 expression through the JNK signaling pathway in human trophoblast-like/trophoblast cells.</p>http://www.rbej.com/content/8/1/5
spellingShingle Wu Xiao-qiu
Li Yu-xia
Cao Bin
Liu Jing
Wang Yan-ling
GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts
Reproductive Biology and Endocrinology
title GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts
title_full GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts
title_fullStr GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts
title_full_unstemmed GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts
title_short GnRH I and II up-regulate MMP-26 expression through the JNK pathway in human cytotrophoblasts
title_sort gnrh i and ii up regulate mmp 26 expression through the jnk pathway in human cytotrophoblasts
url http://www.rbej.com/content/8/1/5
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AT caobin gnrhiandiiupregulatemmp26expressionthroughthejnkpathwayinhumancytotrophoblasts
AT liujing gnrhiandiiupregulatemmp26expressionthroughthejnkpathwayinhumancytotrophoblasts
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