Altered glycolipid metabolism during acute kidney injury exacerbates renal inflammation.

ABSTRACT: Acute kidney injury (AKI) can progress to chronic kidney disease (CKD), via a mechanism that is still largely unknown. We previously reported that glucosylceramide (GlcCer) acts as a damage-associated molecular pattern (DAMP) during AKI. Here, we demonstrate that renal GlcCer levels increase persistently during AKI, primarily due to oxidative stress-mediated downregulation of β-1,4-galactosyltransferase 5 (B4galt5) in proximal tubules. Using mass spectrometry, we showed that GlcCer specifically accumulated in damaged proximal tubules. Among the enzymes involved in GlcCer metabolism, B4galt5 was predominantly expressed in proximal tubules and its expression was consistently downregulated across multiple AKI models. Knockdown of B4galt5 alone was sufficient to increase GlcCer levels in cultu

SUBMITTER: Osada A 

PROVIDER: S-EPMC12765023 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature