AP-2α suppresses invasion in BeWo cells by repression of matrix metalloproteinase-2 and -9 and up-regulation of E-cadherin
Authors: Liting Jia
Shihong Cui
Peng Wang
Ling Zhang
Zhan Zhang
Aimin Chang
Ying Shi
Xianxu Zeng
Journal: Molecular and Cellular Biochemistry (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Preeclampsia; Trophoblasts; AP-2α; TIMP-2; MMP-2
Affiliations: Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 

Abstract:  Preeclampsia complicates 5-10% of pregnancies and is a leading cause of maternal/fetal morbidity and mortality. Although the cause is unknown, the reduced migration/invasion of extravillous trophoblasts is generally regarded as a key feature of preeclampsia genesis. The present study examined the expression of activator protein-2α (AP-2α), tissue inhibitor of metalloproteinase 2 (TIMP-2), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and E-cadherin in severe preeclamptic placentas and normal placentas using real-time PCR and immunohistochemistry. The expression levels of AP-2α, TIMP-2, and E-cadherin were elevated, while MMP-2 and MMP-9 levels were decreased in severe preeclamptic placentas when compared with normal placentas. To explore the underlying molecular mechanisms, BeWo cells were transfected with an AP-2α-expression construct as well as a siRNA against AP-2α. The over-expression of AP-2α decreased the invasive abilities of BeWo cells. AP-2α induction was followed by the induction of TIMP-2 and E-cadherin and a significant reduction of MMP-2 and MMP-9. Whereas in AP-2α-silencing BeWo cells, we observed the decreased expression of TIMP-2 and E-cadherin and the increased expression of MMP-2 and MMP-9. We presume that AP-2α may suppress trophoblast invasion by repression of MMP-2 and MMP-9 and up-regulation of E-cadherin, thus leading to shallow placentation in severe preeclampsia. 

Retracted: No

PubPeer comments:
 This paper is part of a set of papers from the Aix-Marseille Universitu00e9 Institut Hospitalo-Universitaire Mu00e9diterranu00e9e-Infection in Marseille, France, that all describe novel bacterial strains isolated in African countries, but without mentioning ethical approval by local authorities, and without local authors. In this paper, a novel bacterial species is described, isolated from the stool of a healthy 8y old pygmy girl from Congo. The article offers few details, so I hope the authors could answer some questions here. * What was the approximate place of residence of the subject? The text says that the samples were collected in Congo. Do the authors mean ([Republic of the Congo](http: en.wikipedia.org wiki Republic_of_the_Congo) or neighboring [Democratic Republic of the Congo](http: https: en.wikipedia.org wiki Democratic_Republic_of_the_Congo)? * Are there any details known about e.g. diet, living conditions (rural vs urban, agricultural vs. hunter gatherer) of the study subject?There is only limited value to describe a novel human-associated bacterial species if those details about the human host are not given. * The paper cites reference 1, DOI: 10.1128 CMR.00014-14 - but that is a review paper about culturomics and I could not find specific details about the study. Of note, the word Congo is not present in that paper. * Although the first paragraph of the paper states that the samples were collected in Congo, the last paragraph of the paper says the strain was named after Marseille, where the strain was discovered. * The Genbank Entry LT623900 does not mention that the isolate came from a girl in Congo either. Rather it says that it was isolated in the hospital of Timone (Marseille). See: https: www.ncbi.nlm.nih.gov nuccore LT598568 * The link to the MALDI-TOF MS spectrum given in the paper does not seem to be working. I found this link for ALL spectra produced by the institute , but that leads to a downloadable zipped file with files with non-descriptive names such as  EG1 (D9).emf . * How did the authors manage to incubate the specimen in a blood culture bottle under anaerobic conditions? Some details appear to be missing. Was the sample transported from Congo back to France at some cold temperature, and then added to the blood culture bottle, or was the sample processed locally? Did local researchers or authorities participate? * The study mentions *We obtained approval for the study from the ethics committee of the Institut Fu00e9du00e9ratif de Recherches 48 (no. 09-022) before we initiated the project.* But that is a committee in France, not in one of the Congo republics. There is no word about obtaining IRB approval e.g. on consent wording with the local authorities - and no word about consent from the parents. In addition, the authors are from France and Lebanon, without any local researchers to contribute. Could the authors please explain how the research was being performed, and why local researchers were not given a chance to participate? How was this individual selected? ,