DcR3 promotes cell adhesion and enhances endometriosis development

Abstract

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.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2gwQyD7