BMP2 suppresses the production of pentraxin 3 in human endometrial stromal and decidual stromal cells.

Abstract

Bone morphogenetic protein 2 (BMP2) has been shown to act as a critical regulator in the processes of embryo implantation and endometrial decidualization. The expression and production of pentraxin 3 (PTX3) is essential for successful pregnancy, and aberrant production of PTX3 is involved in the pathogenesis of several vascular complications during pregnancy. Studies have shown that several transforming growth factor β superfamily members, including BMP2, can regulate female reproductive function by modulating the expression of PTX3 in human granulosa cells. However, to date, whether BMP2 can regulate the production of PTX3 during endometrial decidualization remains to be elucidated. In this study, we aimed to explore the effect of BMP2 on the expression and production of PTX3 and the underlying molecular mechanisms using immortalized human endometrial stromal cells (I-HESCs) and human decidual stromal cells (HDSCs). We demonstrated that treatment with exogenous BMP2 significantly suppressed PTX3 production by decreasing the mRNA level of PTX3 in both I-HESCs and HDSCs. The results also showed that BMP2 activated SMAD signaling by inducing an increase in the protein levels of phosphorylated SMAD1/5/8, and this effect could be abolished by pretreatment with the ALK2/3 inhibitor DMH-1 but not with the ALK1/4/7 inhibitor SB431542. Additionally, combined knockdown of ALK2 and ALK3 completely reversed the BMP2-induced suppressive effect on PTX3 expression, while concomitant knockdown of SMAD1 and SMAD5 or knockdown of SMAD4 completely reversed the BMP2-induced suppressive effect on PTX3 expression. Taken together, these results indicate that BMP2 suppressed PTX3 production by decreasing PTX expression, which is mediated by a canonical ALK2/3-mediated SMAD1/5-SMAD4-dependent signaling pathway. Our findings suggest that BMP2 may potentially regulate the process of endometrial decidualization by suppressing the production of PTX3 in humans.