Exome sequencing of healthy phenotypic extremes links TROVE2 to emotional memory and PTSD
NATURE HUMAN BEHAVIOUR
Authors: Heck, Angela; Milnik, Annette; Vukojevic, Vanja; Petrovska, Jana; Egli, Tobias; Singer, Jochen; Escobar, Pablo; Sengstag, Thierry; Coynel, David; Freytag, Virginie; Fastenrath, Matthias; Demougin, Philippe; Loos, Eva; Hartmann, Francina; Schicktanz, Nathalie; Bizzini, Bernardo Delarue; Vogler, Christian; Kolassa, Iris-Tatjana; Wilker, Sarah; Elbert, Thomas; Schwede, Torsten; Beisel, Christian; Beerenwinkel, Niko; de Quervain, Dominique J. -F.; Papassotiropoulos, Andreas
Abstract
Many mental disorders represent the extremes of the normal distribution of traits, which are related to multiple cognitive and emotional dimensions. By performing whole-exome sequencing of healthy, young subjects with extremely high versus extremely low aversive memory performance, we identified TROVE2 as a gene implicated in emotional memory in health and disease. TROVE2 encodes Ro60, a broadly expressed RNA-binding protein implicated in the regulation of inflammatory gene expression and autoimmunity. A regulatory TROVE2 variant was linked to higher emotional memory capacity and higher emotional memory-related brain activation in healthy subjects. In addition, TROVE2 was associated with traumatic memory and the frequency of post-traumatic stress disorder in genocide survivors.
TROVE2 strengthens the anti-inflammatory effect via macrophage polarization by estrogen induction in abdominal aortic aneurysm
LIFE SCIENCES
Authors: Chen, Shanshan; Zhao, Yuanyuan; Jin, Huang; Qi, Xiaoyu; He, Jinrong; Huang, Juan; Ding, Yu; Chen, Weiqun; Wu, Chuangyan; Ding, Xiangchao; Chen, Shanshan; Zhang, Hao; Shang, Yuqiang; Du, Dunfeng; Zhao, Jiajia
Abstract
Abdominal Aortic Aneurysm (AAA) is a severe cardiovascular disease, with high mortality rate after acute rupture of blood vessels. However, the underlying pathogenesis of different morbidity between men and women remains unclear. In the present study, we first selected four datasets including 68 AAA and 32 control samples from published data on GEO database, and analyzed them by data mining. The integrative analysis found a total of 368 differentially expressed genes in E2-related AAA. Next, regulatory mechanism networks among these target genes were predicted, and four genes were identified as key nodes in the network, which play a major role in the immune system. We focused on the role of monocytes/macrophages in the development of cardiovascular diseases to further explore the role of estrogen in the polarization of monocytes/macrophage, the mRNA level of the four genes was validated by RT-PCR in RAW264.7 cells treated with beta-estradiol (E2), diarylpropionitrile (DPN), 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), fulvestrant or vehicle. The results showed that the mRNA level and protein level of TROVE2 was significantly increased in estrogen or estrogen receptor agonist-treated groups. Moreover, estrogen affected the transformation of macrophages to M2 phenotype by detecting M1- and M2-related indicator genes at the mRNA level. Flow cytometry demonstrated that the TROVE2 deficiency led to a notable decrease in the level of M2 phenotype marker protein CD206. In conclusion, our results suggest that E2 can promote the expression of TROVE2, which is closely related to the M2-phenotype transformation of macrophages.