World Kidney Day, occurred on March 13th, raises awareness of the important of kidney related researches and therapeutic strategies to fight kidney diseases.
Acute kidney injury (AKI) and chronic kidney disease (CKD) remain significant global health challenges, often driven by inflammation and fibrosis. Emerging studies highlight High-Mobility Group Box 1 (HMGB1) as a key molecular driver in kidney pathological processes, offering new targets for intervention.
HMGB1 and Kidney Fibrosis
Chronic kidney disease (CKD) progression is often linked to fibrosis, where HMGB1 acetylation plays a relevant role. A recent research indicates that the loss of Lgl1, a regulator of epithelial cell polarity, enhances HMGB1 acetylation at lysine 90 (K90), triggering inflammatory cascades.
- The Lgl1 protein negatively regulates SIRT1, a deacetylase that controls HMGB1 acetylation.
- A newly HMGB1-targeted peptide (TAT-K90WT) successfully inhibited HMGB1 acetylation, reducing kidney inflammation and fibrosis. offering a promising avenue for antifibrotic therapy.
These discoveries provide new hope for antifibrotic therapy in CKD, positioning HMGB1 as a viable molecular target for drug development.
HMGB1 and Acute Kidney Injury (AKI): the role of Lactylation
Recent findings reveal that HMGB1 lactylation drives neutrophil extracellular trap (NET) formation in lactate-induced AKI-Acute Kidney Injury: a condition characterized by a sudden decline in renal function, often linked to sepsis, ischemia, and metabolic disturbances.
- HMGB1 lactylation triggers NET formation, amplifying inflammation and worsening kidney damage.
- HMGB1-targeting interventions, such as glycyrrhizin or siRNA, effectively reduce lactate-mediated kidney injury, highlighting HMGB1 as a promising therapeutic target.
Controlling HMGB1 lactylation could be a novel strategy for mitigating AKI severity, particularly in critically ill patients with elevated lactate levels.
As research continues to uncover several roles of HMGB1 in kidney pathology, targeting its post-translational modifications (PTMs) emerges as a promising strategy for nephrology therapeutics.
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Read the full articles about the studies:
https://pubmed.ncbi.nlm.nih.gov/39586505/
https://pubmed.ncbi.nlm.nih.gov/39850900/
