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http://dx.doi.org/10.1038/s12276-018-0167-1

Increased α2-6 sialylation of endometrial cells contributes to the development of endometriosis  

Choi, Hee-Jin (Department of Korean Medical Science, School of Korean Medicine)
Chung, Tae-Wook (Healthy Aging Korean Medical Research Center, Pusan National University)
Choi, Hee-Jung (Healthy Aging Korean Medical Research Center, Pusan National University)
Han, Jung Ho (Department of Korean Medical Science, School of Korean Medicine)
Choi, Jung-Hye (Department of Life and Nanopharmaceutical Sciences and Department of Oriental Pharmacy, Kyung Hee University)
Kim, Cheorl-Ho (Department of Biological Science, Sungkyunkwan University)
Ha, Ki-Tae (Department of Korean Medical Science, School of Korean Medicine)
Publication Information
Experimental and Molecular Medicine / v.50, no.12, 2018 , pp. 9.1-9.12 More about this Journal
Abstract
Endometriosis is a disease characterized by implants of endometrial tissue outside the uterine cavity and is strongly associated with infertility. Focal adhesion of endometrial tissue to the peritoneum is an indication of incipient endometriosis. In this study, we examined the effect of various cytokines that are known to be involved in the pathology of endometriosis on endometrial cell adhesion. Among the investigated cytokines, transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) increased adhesion of endometrial cells to the mesothelium through induction of ${\alpha}2-6$ sialylation. The expression levels of ${\beta}$-galactoside ${\alpha}2-6$ sialyltransferase (ST6Gal) 1 and ST6Gal2 were increased through activation of $TGF-{\beta}RI/SMAD2/3$ signaling in endometrial cells. In addition, we discovered that terminal sialic acid glycan epitopes of endometrial cells engage with sialic acid-binding immunoglobulin-like lectin-9 expressed on mesothelial cell surfaces. Interestingly, in an in vivo mouse endometriosis model, inhibition of endogenous sialic acid binding by a $NeuAc{\alpha}2-6Gal{\beta}1$-4GlcNAc injection diminished $TGF-{\beta}1$-induced formation of endometriosis lesions. Based on these results, we suggest that increased sialylation of endometrial cells by $TGF-{\beta}1$ promotes the attachment of endometrium to the peritoneum, encouraging endometriosis outbreaks.
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