title: Blocking core fucosylation of TGF-β1 receptors downregulates their functions and attenuates the epithelial-mesenchymal transition of renal tubular cells.
abstract: Posttranslational modification of proteins could regulate their multiple biological functions. Transforming growth factor-β receptor I and II (ALK5 and TGF-βRII), which are glycoproteins, play important roles in the renal tubular epithelial-mesenchymal transition (EMT). In the present study, we examined the role of core fucosylation of TGF-βRII and ALK5, which is regulated by α-1,6 fucosyltransferase (Fut8), in the process of EMT of cultured human renal proximal tubular epithelial (HK-2) cells. The typical cell model of EMT induced by TGF-β1 was constructed to address the role of core fucosylation in EMT. Core fucosylation was found to be essential for both TGF-βRII and ALK5 to fulfill their functions, and blocking it with Fut8 small interfering RNA greatly reduced the phosphorylation of Smad2/3 protein, caused the inactivation of TGF-β/Smad2/3 signaling, and resulted in remission of EMT. More importantly, even with high levels of expressions of TGF-β1, TGF-βRII, and ALK5, blocking core fucosylation also could attenuate the EMT of HK-2 cells. Thus blocking core fucosylation of TGF-βRII and ALK5 may attenuate EMT independently of the expression of these proteins. This study may provide new insight into the role of glycosylation in renal interstitial fibrosis. Furthermore, core fucosylation may be a novel potential therapeutic target for treatment of renal tubular EMT.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. wutaihua@sina.com
authors.forename: Hongli
authors.initials: H
authors.lastname: Lin
authors.forename: Dapeng
authors.initials: D
authors.lastname: Wang
authors.forename: Taihua
authors.initials: T
authors.lastname: Wu
authors.forename: Cui
authors.initials: C
authors.lastname: Dong
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yanling
authors.initials: Y
authors.lastname: Sun
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Lujuan
authors.initials: L
authors.lastname: Shan
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005647:Fucosyltransferases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005647:Fucosyltransferases