Gadd45a knockdown alleviates oxidative stress through suppressing the p38 MAPK signaling pathway in the pathogenesis of preeclampsia
Authors: Qian Xu
Na Han
Yong Wang
Fa-Hong Li
Journal: Placenta (2018)
Discipline: CLINICAL MEDICINE
Keywords: Gene silencing; Growth arrest and DNA damage gene 45 alpha; Oxidative stress; Preeclampsia; Small interfering RNA
Affiliations: Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, 266034, PR China., Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, 266034, PR China. Electronic address: .

Abstract:  Objective: Preeclampsia (PE) is a hypertensive disease associated with vascular oxidative stress (OS). Besides, cell response to OS triggers growth arrest and DNA damage inducible alpha (Gadd45a). Herein, we investigated the effect of Gadd45a on OS in PE. Methods: Umbilical cord tissues and peripheral blood samples were collected from PE patients and normal pregnant women. Immunohistochemistry was applied to identify Gadd45a level and extent of p38 phosphorylation. To verify the effect of Gadd45a on CRL1730 human umbilical vein endothelial cell (HUVEC) behavior, HUVECs were treated with hypoxia/reoxygenation (H/R) and Gadd45a-siRNA or P79350. OS products were detected using thiobarbituric acid-reactive-substance assay, immune enzyme assay, enzyme-linked immunosorbent assay (ELISA) and super oxide dismutase (SOD) kit. HUVEC behaviors were evaluated using flow cytometry, wound-healing test, and Transwell assay. The tube formation ability was assessed using in vitro tube formation assay. Results: PE umbilical cord tissues exhibited increased Gadd45a expression, extent of p38 phosphorylation, 8-isoprostane and oxidatively modified low density lipoprotein (Ox-LDL) and decreased SOD levels. HUVECs treated with H/R or agonist + H/R showed similar expression tendencies of related genes, enhanced apoptosis and inhibited migration, invasion, and blood vessel formation. Gadd45a-siRNA conferred alleviation to OS with decreased apoptosis, greater cell migration, invasion and blood vessel, which appeared to be weakened by treatment of Gadd45a siRNA + P79350. Conclusion: Over-expression of Gadd45a and activation of the p38 MAPK signaling pathway are associated with OS in PE. Furthermore, Gadd45a knockdown promotes cell migration and invasion, and the tube formation, thus alleviating OS in PE. 

Retracted: No

PubPeer comments:
  Fig. 4. Flow cytometric detection for the effect of Gadd45a on cell apoptosis. I can only suppose that there was a glitch during the selection of files to be included in a PDF which led to the superimposition of a 7th scatterplot as well as the six that were desired. No-one in the process of paper preparation saw anything wrong with the result.  Even more surprising, the nearest match to extraneous scatterplot is this panel from Fig 7C of [Cai et al (2017)] .  Unless it was an identical panel from Fig 11A of [Shang et al (2018) .  It is not immediately obvious why anyone involved in the preparation of this figure should have the image files from Cai et al **or** Shang et al sitting around on their computer. , 
 Fig 3B.  The Western Blots in this paper all seem to come from a restricted gamut of protein-blob shapes, used in a number of papers from different authors, as in this montage I prepared earlier.  , 
 Fig 1A. An unusual symmetry with the two VE-cadherin slides.  At the risk of flogging a dead horse, I will point out some implausibly repeated features within other panels of the Figure. The remaining panels are left as an exercise for the reader.  ,