Down-regulation of TAGLN2 associated with the development of preeclampsia by effecting the Rap1 signaling pathway.

INTRODUCTION

Preeclampsia (PE) poses significant global challenges to pregnancy health, being a leading cause of maternal and perinatal morbidity and mortality. Unfortunately, effective treatment options remain limited, necessitating the urgent development of novel therapeutic strategies. This study is to investigate down-regulation of Transgelin-2 (TAGLN2) contributes to the development of PE through suppression of the Rap1 signaling pathway.

METHODS

Placentas from PE patients were collected for a transcriptome analysis. Down-regulation experiments of TAGLN2 were performed in mouse and HTR-8/SVneo cells to generate PE models. The mechanism by which down-regulation of TAGLN2 induces PE was explored based on these PE model through transcriptome and proteome analysis and molecular tests.

RESULTS

Our findings revealed that the expression levels of Rap1A was significantly reduced in the placenta of PE patients. The expression level of Rap1A in the placental tissue of sh_Tagln2 PE model mice is down-regulated. In addition, TAGLN2 down-regulation impede the proliferation and migration of HTR8/SVneo cells and lead to the decreased expression of Rap1A. Meanwhile, Rap1A down-regulation impede both the proliferation and migration of HTR8/SVneo cells. Both transcriptomic and proteomic levels of sh-TG2 HTR8/SVneo cells demonstrated Rap1 signaling pathway and related key genes was inhibited after TAGLN2 down-regulation.

CONCLUSION

Our results confirm that down-regulation of TAGLN2 in HTR-8/SVneo cells leads to the decreased Rap1A expression and suppresses trophoblast cell proliferation and migration by inhibiting Rap1 signaling pathway. Meanwhile, Rap1A down-regulation impede both the proliferation and migration of HTR8/SVneo cells. These findings concluded that down-regulation of TAGLN2 may be implicated in the development of preeclampsia through its effect on the Rap1 signaling pathway.