DcR3 promotes cell adhesion and enhances endometriosis development.

Endometriosis is a multifactorial inflammatory disease with persistent activation of NF-κB signaling pathway. Aberrant adhesion of endometrium is the essential step in the progression of endometriosis, but the molecular mechanism for ectopic growth of endometrium is still unclear. Decoy receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by estrogen, is able to activate focal adhesion kinase (FAK) to promote cell adhesion. We found that DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt/NF-κB signaling pathway, and its expression level correlates positively with that of adhesion molecules ICAM-1 (intercellular adhesion molecule 1) and HCAM (homing cell adhesion molecule, CD44). In a multivariate regression model, DcR3 expression level was the most significant parameter associated with endometriosis severity. Knockdown of DcR3 not only downregulated the expression of ICAM-1 and HCAM, but also reduced cell adhesion and migration. In vivo study further showed that DcR3 promoted the growth and spreading of endometrium, while knockdown of DcR3 by lentivirus-delivered shRNA inhibited ectopic adhesion of endometrium and abrogated endometriosis progression. These observations support that DcR3 plays a critical role in the pathogenesis of endometriosis, and that the inhibition of DcR3 expression is a promising approach for the treatment of endometriosis. This article is protected by copyright. All rights reserved.

Citation

Hsiao-Wen Tsai, Ming-Ting Huang, Peng-Hui Wang, Ben-Shian Huang, Yi-Jen Chen, Shie-Liang Hsieh. DcR3 promotes cell adhesion and enhances endometriosis development. The Journal of pathology. 2017 Oct 23

PMID: 29057478

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