Tags

Type your tag names separated by a space and hit enter

Blocking core fucosylation of TGF-β1 receptors downregulates their functions and attenuates the epithelial-mesenchymal transition of renal tubular cells.
Am J Physiol Renal Physiol. 2011 Apr; 300(4):F1017-25.AJ

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+Show Affiliations

Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. wutaihua@sina.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21228108

Citation

Lin, Hongli, et al. "Blocking Core Fucosylation of TGF-β1 Receptors Downregulates Their Functions and Attenuates the Epithelial-mesenchymal Transition of Renal Tubular Cells." American Journal of Physiology. Renal Physiology, vol. 300, no. 4, 2011, pp. F1017-25.
Lin H, Wang D, Wu T, et al. Blocking core fucosylation of TGF-β1 receptors downregulates their functions and attenuates the epithelial-mesenchymal transition of renal tubular cells. Am J Physiol Renal Physiol. 2011;300(4):F1017-25.
Lin, H., Wang, D., Wu, T., Dong, C., Shen, N., Sun, Y., Sun, Y., Xie, H., Wang, N., & Shan, L. (2011). Blocking core fucosylation of TGF-β1 receptors downregulates their functions and attenuates the epithelial-mesenchymal transition of renal tubular cells. American Journal of Physiology. Renal Physiology, 300(4), F1017-25. https://doi.org/10.1152/ajprenal.00426.2010
Lin H, et al. Blocking Core Fucosylation of TGF-β1 Receptors Downregulates Their Functions and Attenuates the Epithelial-mesenchymal Transition of Renal Tubular Cells. Am J Physiol Renal Physiol. 2011;300(4):F1017-25. PubMed PMID: 21228108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blocking core fucosylation of TGF-β1 receptors downregulates their functions and attenuates the epithelial-mesenchymal transition of renal tubular cells. AU - Lin,Hongli, AU - Wang,Dapeng, AU - Wu,Taihua, AU - Dong,Cui, AU - Shen,Nan, AU - Sun,Yuan, AU - Sun,Yanling, AU - Xie,Hua, AU - Wang,Nan, AU - Shan,Lujuan, Y1 - 2011/01/12/ PY - 2011/1/14/entrez PY - 2011/1/14/pubmed PY - 2011/7/2/medline SP - F1017 EP - 25 JF - American journal of physiology. Renal physiology JO - Am J Physiol Renal Physiol VL - 300 IS - 4 N2 - 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. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/21228108/Blocking_core_fucosylation_of_TGF_β1_receptors_downregulates_their_functions_and_attenuates_the_epithelial_mesenchymal_transition_of_renal_tubular_cells_ L2 - https://journals.physiology.org/doi/10.1152/ajprenal.00426.2010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -