HNRNPK Lactylation Amplifies Inflammation and Exacerbates Myocardial Ischemia/Reperfusion Injury by Regulating Jag2 Splicing.

Lactylation of HNRNPK at lysine 405 in myocardium increases after reperfusion and promotes Jag2 splicing changes that exacerbate inflammation and injury.

• Why it matters: Understanding how metabolic stress influences inflammatory gene expression is crucial for developing targeted therapies for ischemia/reperfusion injury, which involves lactate accumulation and inflammation.
• What they did: Researchers analyzed human and murine heart tissues, used proteomics, RNA sequencing, and mutagenesis to identify HNRNPK lactylation at K405, and tested interventions like antisense oligonucleotides in mice and cardiomyocytes.
• The result: HNRNPK lactylation at K405 shifts Jag2 splicing toward the long isoform, activating Notch-NF-κB signaling and worsening injury; blocking this interaction reduces inflammation and preserves cardiac function.