Inhibition of lysyl oxidase by prostaglandin E2 via EP2/EP4 receptors in human amnion fibroblasts: Implications for parturition
Inhibition of lysyl oxidase by prostaglandin E2 via EP2/EP4 receptors in human amnion fibroblasts: Implications for parturition
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前列腺素 E2 通过 EP2/EP4 受体抑制人羊膜成纤维细胞中的赖氨酰氧化酶：对分娩的影响
DOI：
10.1016/j.mce.2016.01.022
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发表时间：
2016-03
影响因子：
4.1
通讯作者：
Sun Kang
中科院分区：
文献类型：
--
作者：
Liu Chao;Zhu Ping;Wang Wangsheng;Li Wenjiao;Shu Qun;Chen Zi-Jiang;Myatt Leslie;Sun Kang
导致分娩时胎膜破裂的潜在机制尚不完全清楚。赖氨酰氧化酶（LOX）交联胶原纤维，从而增加膜的拉伸强度。因此，了解LOX表达的调控可能是至关重要的，阐明的过程中，胎膜破裂。前列腺素E2（PGE 2）主要由羊膜产生，在人类分娩过程中起着至关重要的作用。然而，目前尚不清楚PGE 2是否调节LOX在胎膜中的表达。使用原代人羊膜成纤维细胞，我们发现，除了PGE 2降低LOX mRNA和蛋白水平，这是通过抑制EP 2/EP 4受体和受体偶联cAMP/PKA途径阻断。EP 2/EP 4受体激动剂和cAMP/PKA通路的刺激剂一致地降低LOX表达。此外，PGE 2通过EP 2和EP 4受体偶联的cAMP/PKA途径诱导环加氧酶-2（考克斯-2）表达，COX-2是PGE 2产生的关键酶。小干扰RNA介导的考克斯-2表达的敲低显著增加LOX的基础表达。此外，在足月分娩后，羊膜组织中考克斯-2的表达增加，LOX的丰度相应降低。总之，我们揭示了一个前馈回路的诱导考克斯-2和减少LOX表达的PGE 2通过EP 2/EP 4受体偶联cAMP/PKA途径在人羊膜成纤维细胞作用于妊娠末期，这可能在胎膜破裂中发挥重要作用。
The underlying mechanism leading to rupture of the membranes at parturition is not fully understood. Lysyl oxidase (LOX) cross-links collagen fibrils thereby increasing the tensile strength of the membranes. Thus, understanding the regulation of LOX expression may be of crucial importance for elucidation of the process of rupture of the fetal membranes. Prostaglandin E2 (PGE2), mainly produced in the amnion, plays crucial roles during human parturition. However it is not known whether PGE2 regulates LOX expression in the fetal membranes. Using primary human amnion fibroblasts, we showed that addition of PGE2 decreased LOX mRNA and protein levels, which were blocked by inhibition of EP2/EP4 receptors and the receptor-coupled cAMP/PKA pathway. EP2/EP4 receptor agonists and stimulators of the cAMP/PKA pathway consistently decreased LOX expression. Furthermore, PGE2 induced cyclo-oxygenase-2 (COX-2) expression, a key enzyme in PGE2 production, via an EP2 and EP4 receptor-coupled cAMP/PKA pathway. Small interfering RNA-mediated knock-down of COX-2 expression significantly increased the basal expression of LOX. In addition, an increase in COX-2 and a reciprocal decrease in LOX abundance occurred in amnion tissue following labor at term. In conclusion, we have revealed a feed-forward loop of induction of COX-2 and reduction in LOX expression by PGE2 acting via an EP2/EP4 receptor-coupled cAMP/PKA pathway in human amnion fibroblasts toward the end of gestation, which may play a significant role in the rupture of fetal membranes.
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影响因子：
4.8
作者：
Faour, Wissam H.;Gomi, Kaede;Kennedy, Christopher R. J.
通讯作者：
Kennedy, Christopher R. J.
DOI：
10.1016/s0090-6980(75)80113-4
发表时间：
1975
期刊：
Prostaglandins
影响因子：
--
作者：
W. L. Miller;J. Weeks;J. Lauderdale;K. Kirton
通讯作者：
W. L. Miller;J. Weeks;J. Lauderdale;K. Kirton
影响因子：
3.6
作者：
J. Regan;T. Bailey;D. J. Pepperl;K. L. Pierce;A. Bogardus;J. Donello;C. E. Fairbairn;K. Kedzie;D. Woodward;D. Gil
通讯作者：
J. Regan;T. Bailey;D. J. Pepperl;K. L. Pierce;A. Bogardus;J. Donello;C. E. Fairbairn;K. Kedzie;D. Woodward;D. Gil
DOI：
10.1210/jcem.87.3.8320
发表时间：
2002-03
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
P. Xu;N. Alfaidy;J. Challis
通讯作者：
P. Xu;N. Alfaidy;J. Challis
DOI：
10.1172/jci37785
发表时间：
2008-12
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Michael J. Taggart;G. Nicholas Europe-Finner;Bryan F. Mitchell
通讯作者：
Michael J. Taggart;G. Nicholas Europe-Finner;Bryan F. Mitchell