FUT1-mediated terminal fucosylation acts as a new target to attenuate renal fibrosis

Abstract

Backgrounds Renal fibrosis is a common pathologic process of most chronic kidney diseases (CKDs), becoming one of the major public health problems worldwide. Terminal fucosylation plays an important role in physiological homeostasis and pathological development. The present study aimed to explore the role of terminal fucosylation during kidney fibrogenesis and propose a possible anti-fibrosis treatment via suppressing aberrant terminal fucosylation. Methods We investigated the expression level of fucosyltransferase1 (FUT1) in CKD patients by using public database. Then, we further confirmed the level of terminal fucosylation by UEA-I staining and FUT1 expression in unilateral ureteral obstruction (UUO)-induced renal fibrosis mice. Immunostaining, qPCR, western blotting and wound healing assay were applied to reveal the effect of FUT1 overexpression in human kidney proximal tubular epithelial cell (HK-2). What’s more, we applied terminal fucosylation inhibitor, 2-Deoxy-D-galactose (2-D-gal), to determine whether suppressing terminal fucosylation ameliorates renal fibrosis progression in vitro and in vivo. Results Here, we found that the expression of FUT1 significantly increased during renal fibrosis. In vitro experiments showed upregulation of epithelial-mesenchymal transition (EMT) after over-expression of FUT1 in HK-2. Furthermore, in vivo and in vitro experiments indicated that suppression of terminal fucosylation, especially on TGF-βR I and II, could alleviate fibrogenesis via inhibiting transforming growth factor-β (TGF-β)/Smad signaling. Conclusions The development of kidney fibrosis is attributed to FUT1-mediated terminal fucosylation, shedding light on the inhibition of terminal fucosylation as a potential therapeutic treatment against renal fibrosis.

Insights into protein fucosylation in insects

“…Alteration in the fucosylation profile is clinically used as an indicator for diseases. For example, the expression of FucTs or the fucosylation profile of proteins can be used as prognostic marker and therapeutic target for cancer patients (Geng et al 2004, Loong et al 2021, Luo et al 2023. The fucosylation of antibodies also plays an important role in the treatment or diagnosis of diseases (Bournazos et al 2021, Wang & Ravetch 2019.…”