TIG1 triggers placental senescence in preeclampsia through LMNA/p53 axis activation.

Abstract

Introduction: The mechanism behind abnormal placental aging in preeclampsia (PE) is unclear. Although TIG1 is widely expressed in the human placenta, its function hasn't been well understood. Our previous study found a significant elevation of TIG1 in the placentas of PE patients. In this study, we focused on the molecular mechanism by which TIG1 functions in PE.

Methods: TIG1 expression of placentas from PE patients and L-NAME mice were analyzed using qRT-PCR, Western blot, and immunohistochemistry. TIG1-overexpressed HTR-8/SVneo cells were constructed for transcriptomic sequencing. Senescence in the placenta was evaluated by biomarkers of p16, p21, and p53. TIG1 binding proteins were identified via co-immunoprecipitation. A co-culture system of HTR-8/SVneo and human endometrial stromal cells was developed to study the change in trophoblasts' function.

Results: TIG1 expression was significantly increased in the PE placentas. Elevated expression of TIG1 was associated with abnormal senescence of trophoblasts. TIG1 induced trophoblasts' senescence by regulating LMNA/p53 axis. The senescence of trophoblasts can be manifested as reduced invasion ability in the co-culture system.

Discussion: Our study indicated that TIG1 was crucial in the development of PE by causing the senescence of trophoblasts and reducing their invasiveness, offering insights into the molecular mechanisms of placental dysfunction in PE.