Lactate: a missing link between metabolism and inflammation in CKD progression?

Area of Science:

• Nephrology
• Molecular Biology
• Biochemistry

Background:

• Persistent enhancement of glycolysis in kidney tubular epithelial cells is associated with chronic kidney disease (CKD) progression.
• The precise molecular mechanisms linking glycolysis to kidney fibrosis remain largely unknown.
• Understanding these mechanisms is crucial for developing effective CKD treatments.

Purpose of the Study:

• To investigate the role of the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in kidney fibrosis.
• To elucidate the molecular pathways through which PFKFB3 contributes to kidney fibrosis.
• To assess the therapeutic potential of inhibiting PFKFB3 in kidney fibrosis.

Main Methods:

• The study by Wang et al. focused on the glycolytic enzyme PFKFB3.
• They investigated the link between PFKFB3, lactate accumulation, histone H4 lysine 12 lactylation, and nuclear factor-κB (NF-κB) signaling.
• Experimental inhibition of PFKFB3 was employed to evaluate its effects on kidney fibrosis.

Main Results:

• PFKFB3 enhances kidney fibrosis by increasing lactate accumulation.
• This lactate accumulation promotes histone H4 lysine 12 lactylation.
• PFKFB3 activity leads to increased transcription of NF-κB-related genes, promoting inflammation and fibrosis.
• Inhibition of PFKFB3 was shown to reduce these pro-fibrotic and inflammatory effects.

Conclusions:

• PFKFB3 plays a critical role in kidney fibrosis through the enhancement of histone lactylation and NF-κB activation.
• Targeting PFKFB3 presents a promising therapeutic strategy for mitigating kidney fibrosis and inflammation in CKD.
• Further research into PFKFB3 inhibition could lead to novel treatments for chronic kidney disease.