Ten-eleven translocation 2 demethylates the MMP9 promoter, and its down-regulation in preeclampsia impairs trophoblast migration and invasion.

The Journal of Biological Chemistry
Xiaoliang LiWenming Xu

Abstract

Preeclampsia is the most common clinical disorder in pregnancy and might result from disordered uterine environments caused by epigenetic modifications, including deregulation of DNA methylation/demethylation. Recent research has indicated that 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (TET) enzymes, is involved in DNA methylation-related plasticity. Here, we report that TET2 expression and 5hmC abundance are significantly altered in the placentas from preeclampsia patients. shRNA-mediated TET2 knockdown (shTET2) reduced trophoblast migration and invasion when cultured in Matrigel. Both real-time PCR of matrix metalloproteinase (MMP)-related transcripts and a human angiogenesis antibody array indicated that TET2 knockdown in trophoblasts inhibits the expression of MMP transcript, of which MMP9 represented one of the most significant TET2 downstream targets. Using an established shTET2 HTR-8/SVneo cell model, we further confirmed alterations of 5hmC levels and MMP9 expression at both mRNA and protein levels. In particular, we found that TET2 bound to and removed 5mC modifications at the MMP9 promoter region. Interestingly, in TET2 knockdown cells, bot...Continue Reading

References

Oct 20, 2010·Acta Clinica Belgica·S LorquetJ M Foidart
Oct 21, 2010·Human Reproduction Update·Ewka C M NelissenJohannes L H Evers
Feb 18, 2011·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Wen-long GaoYan-ling Wang
Jun 9, 2012·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·Cilia AbadFulgencio Proverbio
Jan 23, 2013·Hypertension·Vijayakumar ChinnathambiKunju Sathishkumar
Feb 19, 2013·Journal of Molecular Endocrinology·Li LingLi Yan
Jun 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Vicki PlaksZena Werb
Jun 21, 2013·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·Wendy M WhiteVesna D Garovic
Oct 30, 2013·Biological Research for Nursing·Cindy M AndersonJoyce E Ohm
Jul 9, 2014·Nature Reviews. Nephrology·Tinnakorn ChaiworapongsaRoberto Romero
Jul 16, 2014·The International Journal of Developmental Biology·Satoshi TanakaKunio Shiota
Aug 1, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sathnur PushpakumarUtpal Sen
Dec 15, 2015·Molecular Human Reproduction·Bo PengPeter C K Leung
Feb 26, 2016·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Jinglu ZhangLi Yan
Feb 28, 2016·Clinical Endocrinology·Qin TanMeng Ren
Mar 24, 2016·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Minghua FanXingbo Zhao
Apr 3, 2016·Genes & Development·Kasper Dindler Rasmussen, Kristian Helin
Jul 28, 2016·Laboratory Investigation; a Journal of Technical Methods and Pathology·Renu A KowluruManish Mishra
Feb 14, 2017·International Journal of Biological Macromolecules·Kai QuZuo Wang
Mar 1, 2017·Cold Spring Harbor Perspectives in Medicine·Robert L Bowman, Ross L Levine
Apr 20, 2017·American Journal of Respiratory and Critical Care Medicine·Lyndsey E Shorey-KendrickEliot R Spindel
Apr 30, 2017·Experimental & Molecular Medicine·Jungeun AnMyunggon Ko
May 10, 2017·Reproduction : the Official Journal of the Society for the Study of Fertility·Li TangWenming Xu
Aug 22, 2017·Nature·Michalis AgathocleousSean J Morrison
Dec 21, 2017·Investigative Ophthalmology & Visual Science·Arul J DuraisamyRenu A Kowluru

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Citations

Jun 20, 2019·International Journal of Molecular Sciences·Clara ApicellaDaniel Vaiman
Jul 26, 2019·BioFactors·Amin KamraniMajid Ahmadi
Aug 9, 2019·The Journal of Clinical Endocrinology and Metabolism·Angela S KelleyVasantha Padmanabhan
Apr 3, 2021·Frontiers in Pharmacology·Jingtao JiangWeiyang Gao
Oct 14, 2021·Clinical Science·Usman M AshrafBarbara T Alexander

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