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ID3 mediates BMP2-induced downregulation of ICAM1 expression in human endometiral stromal cells and decidual cells

Recurrent pregnancy loss (RPL) remains an unsolved problem in obstetrics and gynecology, and up to 50% of RPL cases are unexplained. Unexplained RPL (uRPL) is widely considered to be related to an aberrant endometrial microenvironment. BMP2 is an important factor involved in endometrial decidualization and embryo implantation, and intercellular adhesion molecule 1 (ICAM1) is a critical inflammatory regulator in the endometrium. In this study, we found that endometrial samples obtained from Unexplained RPL patients have significantly lower BMP2 and higher ICAM1 levels than fertile controls. For further research on the relationship between BMP2 and ICAM1 and the potential molecular mechanisms in Unexplained RPL, immortalized human endometrial stromal cells (HESCs) and primary human decidual stromal cells (HDSCs) were used as study models. Our results showed that BMP2 significantly decreased ICAM1 expression by upregulating DNA-binding protein inhibitor 3 (ID3) in both HESCs and HDSCs. Using kinase receptor inhibitors (dorsomorphin homolog 1 (DMH-1) and dorsomorphin) and siRNA transfection, it has been found that the upregulation of ID3 and the following downregulation of ICAM1 induced by BMP2 is regulated through the ALK3-SMAD4 signaling pathway. This research gives a hint of a novel mechanism by which BMP2 regulates ICAM1 in the human endometrium, which provides insights into potential therapeutics for unexplained RPL.

 

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This study suggests that unexplained recurrent pregnancy loss (uRPL) may be related to an abnormal endometrial microenvironment characterized by lower BMP2 and higher ICAM1 levels. BMP2 is an essential factor involved in endometrial decidualization and embryo implantation, while ICAM1 is a crucial regulator of inflammation in the endometrium. The study investigated the relationship between BMP2 and ICAM1 and the potential molecular mechanisms involved in uRPL using human endometrial stromal cells.

The findings indicate that BMP2 significantly reduces ICAM1 expression by increasing the levels of DNA-binding protein inhibitor 3 (ID3) in both HESCs and HDSCs. The study further reveals that the upregulation of ID3 and the subsequent downregulation of ICAM1 induced by BMP2 is regulated through the ALK3-SMAD4 signaling pathway. These results suggest a new mechanism by which BMP2 regulates ICAM1 in the human endometrium, which could have implications for the development of potential therapeutics for uRPL.

Overall, this study sheds light on the underlying mechanisms of uRPL, which remains a significant challenge in obstetrics and gynecology. The findings may have important clinical implications for the management and treatment of uRPL. However, further studies are necessary to validate these findings and explore potential clinical applications.

Related Products

Cat.No. Product Name Information
S7146 DMH1 DMH1 is a selective BMP receptor inhibitor with IC50 of 107.9 nM for ALK2, exhibiting no inhibition on AMPK, ALK5, KDR (VEGFR-2) or PDGFR. DMH1 inhibits autophagy.

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Autophagy TGF-beta/Smad