METTL3 mediated m6A modification of HKDC1 promotes renal injury and inflammation in lead nephropathy.

ABSTRACT: Environmental and industrial Pb exposure poses a significant public health challenge. Acute exposure to high Pb concentrations can result in renal injury. Here, we revealed that N6-methyladenosine (m6A) RNA methylation was significantly upregulated in lead nephropathy and was mainly mediated by the methyltransferase METTL3. Functionally, METTL3 knockout in renal tubular epithelial cells or AAV9-mediated METTL3 silencing alleviated renal injury and the inflammatory response induced by lead acetate. METTL3 silencing in renal tubular epithelial cells reduced both m6A RNA methylation and inflammatory responses following lead acetate treatment. We identified hexokinase domain-containing 1 (HKDC1), known to function in the glycolytic pathway, as a direct METTL3 target. Importantly, HKDC1 was upr

SUBMITTER: Suo XG 

PROVIDER: S-EPMC12160926 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature