Loss of FUT8 in renal tubules ameliorates ischemia‐reperfusion injury‐induced renal interstitial inflammation transition to fibrosis via the TLR3–NF‐κB pathway

Renal ischemia‐reperfusion injury (IRI) is a common reason of acute kidney injury (AKI). AKI can progress to chronic kidney disease (CKD) in some survivors. Inflammation is considered the first‐line response to early‐stage IRI. We previously reported that core fucosylation (CF), specifically catalyzed by α‐1,6 fucosyltransferase (FUT8), exacerbates renal fibrosis. However, the FUT8 characteristics, role, and mechanism in inflammation and fibrosis transition remain unclear. Considering renal tubular cells are the trigger cells that initiate the fibrosis in the AKI‐to‐CKD transition in IRI, we targeted CF by generating a renal tubular epithelial cell (TEC)‐specific FUT8 knockout mouse and measured FUT8‐driven and downstream signaling pathway expression and AKI‐to‐CKD transition. During the IRI extension phase, specific FUT8 deletion in the TECs ameliorated the IRI‐induced renal interstitial inflammation and fibrosis mainly via the TLR3 CF–NF‐κB signaling pathway. The results firstly indicated the role of FUT8 in the transition of inflammation and fibrosis. Therefore, the loss of FUT8 in TECs may be a novel potential strategy for treating AKI–CKD transition. TEC‐specific FUT8 deletion ameliorates renal fibrosis induced by IRI through the TLR3 CF–NF‐κB pathway.