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

Abstract

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.