Drastic induction of MMP-7 by cortisol in the human amnion: implications for membrane rupture at parturition
Drastic induction of MMP-7 by cortisol in the human amnion: implications for membrane rupture at parturition
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人羊膜中皮质醇对 MMP-7 的强烈诱导：对分娩时胎膜破裂的影响
DOI：
10.1096/fj.201801216r
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Ying Hao
中科院分区：
文献类型：
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作者：
Wang Lu Yao;Wang Wang Sheng;Wang Ya Wei;Lu Jiang Wen;Lu Yi;Zhang Chu Yue;Li Wen Jiao;Sun Kang;Ying Hao
30-40%的早产发生于胎膜早破。基质金属蛋白酶（MMPs）的活化是膜破裂过程中细胞外基质（ECM）降解的主要原因之一。分娩时羊膜中11β -羟基类固醇脱氢酶1再生的皮质醇升高，参与了许多分娩相关事件。然而，皮质醇是否在膜中MMPs的调节中起作用尚不清楚。在这里，我们用人羊膜组织来解决这个问题，羊膜是膜中最具张力的一层。RNA测序显示，皮质醇显著诱导羊膜成纤维细胞中mmp7的表达，这在皮质醇处理的羊膜外植体和成纤维细胞中得到了实时定量RT - PCR和Western blotting分析的证实。胶原IV α5链（COL4A5）是MMP‐7的底物，测量结果表明，皮质醇降低了其细胞外丰度，这被抗MMP‐7的抗体阻断。此外，分娩引起的羊膜自发破裂后，羊膜组织中MMP‐7增加，COL4A5丰度减少。机制研究表明，皮质醇分别增加了活化蛋白1 （AP - 1）的两种主要成分c‐Jun的磷酸化和c‐Fos的表达。c‐Fos或c‐Jun的下调显著减弱了皮质醇对mmp7表达的诱导。染色质免疫沉淀实验显示，皮质醇刺激themmp7启动子AP - 1结合位点的c‐Fos和c‐Jun的富集。这些数据表明，皮质醇- 1诱导mmp7可能是分娩时膜破裂时ECM降解的一个促进因素。王,l . Y。王伟。王玉文，王玉文。卢杰。，卢勇，张春英。李伟，李文杰。孙凯，应辉。皮质醇对人羊膜MMP - 7的诱导作用：对分娩时羊膜破裂的影响。中国生物医学工程学报，2016,32(2):444 - 444。www.fasebj.org
Preterm premature rupture of fetal membranes precedes 30–40% of preterm births. Activation of matrix metalloproteases (MMPs) is the one of the major causes of extracellular matrix (ECM) degradation in membrane rupture. Increased cortisol, regenerated by 11β‐hydroxysteroid dehydrogenase 1 in the amnion at parturition, is known to participate in a number of parturition‐pertinent events. However, whether cortisol has a role in the regulation of MMPs in the membranes is not known. Here, we addressed this issue using human amnion tissue, the most tensile layer of the membranes. RNA‐sequencing revealed that cortisol inducedMMP7expression dramatically in amnion fibroblasts, which was confirmed by real‐time quantitative RT‐PCR and Western blotting analysis in cortisol‐treated amnion explants and fibroblasts. Measurement of collagen IV α5 chain (COL4A5), a substrate for MMP‐7, showed that cortisol reduced its extracellular abundance, which was blocked by an antibody against MMP‐7. Moreover, increased MMP‐7 but decreased COL4A5 abundance was observed in the amnion tissue following labor‐initiated spontaneous rupture of membranes. Mechanistic studies showed that cortisol increased the phosphorylation of c‐Jun and the expression of c‐Fos, the 2 major components of activated protein 1 (AP‐1), respectively. The knocking down of c‐Fos or c‐Jun significantly attenuated the induction ofMMP7expression by cortisol. Chromatin immunoprecipitation assays showed that cortisol stimulated the enrichment of c‐Fos and c‐Jun at the AP‐1 binding site in theMMP7promoter. The data suggest that induction ofMMP7by cortisolviaAP‐1 may be a contributing factor to ECM degradation in membrane rupture at parturition.—Wang, L.‐Y., Wang, W.‐S., Wang, Y.‐W., Lu, J.‐W., Lu, Y., Zhang, C.‐Y., Li, W.‐J., Sun, K., Ying, H. Drastic induction of MMP‐7 by cortisol in the human amnion: implications for membrane rupture at parturition. FASEB J. 33, 2770–2781 (2019). www.fasebj.org