Molecular immunology · 2025
ZBTB16 promotes the transcription of glycolytic enzyme PFKFB2 to participate in fibrogenesis in septic lung injury.
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Tai Zijian, Wang Chunting
Аннотация
BACKGROUND: Sepsis is a severe systemic inflammatory response syndrome that leads to acute lung injury (ALI), which subsequently progresses to lung fibrosis. This study aims to investigate the role of zinc finger and BTB domain containing 16 (ZBTB16), a transcription factor, in septic lung injury.
METHODS: The expression of Zbtb16 in the injured lung was evaluated using single-cell sequencing. The signaling pathways that can be regulated by Zbtb16 were predicted using gene set enrichment analysis (GSEA). Then, the functions of ZBTB16 and its potential molecular mechanism in fibrogenesis were explored in lipopolysaccharide (LPS)-induced ALI mice in vivo and LPS-induced MRC-5 cells and primary fibroblasts in vitro.
RESULTS: Single-cell analysis showed that Zbtb16 was overexpressed in the fibroblasts of the injured lung. GSEA found that Zbtb16 might activate inflammatory response and glycolysis during lung injury. Silencing of Zbtb16 relieved lung injury, decreased lung wet/dry weight and myeloperoxidase (MPO) activity, reduced the levels of lactate dehydrogenase (LDH), total protein, and neutrophil in the BALF, and inhibited fibrogenesis in septic ALI mice. In LPS-induced fibroblasts, silencing of ZBTB16 suppressed the expression of inflammatory and fibrotic markers by inhibition of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2)-mediated glycolysis.
CONCLUSION: ZBTB16 promotes the transcription of glycolytic enzyme PFKFB2 to participate in fibrogenesis in septic lung injury. Our study may offer a potentially promising target for the treatment of fibrogenesis in septic lung injury.
METHODS: The expression of Zbtb16 in the injured lung was evaluated using single-cell sequencing. The signaling pathways that can be regulated by Zbtb16 were predicted using gene set enrichment analysis (GSEA). Then, the functions of ZBTB16 and its potential molecular mechanism in fibrogenesis were explored in lipopolysaccharide (LPS)-induced ALI mice in vivo and LPS-induced MRC-5 cells and primary fibroblasts in vitro.
RESULTS: Single-cell analysis showed that Zbtb16 was overexpressed in the fibroblasts of the injured lung. GSEA found that Zbtb16 might activate inflammatory response and glycolysis during lung injury. Silencing of Zbtb16 relieved lung injury, decreased lung wet/dry weight and myeloperoxidase (MPO) activity, reduced the levels of lactate dehydrogenase (LDH), total protein, and neutrophil in the BALF, and inhibited fibrogenesis in septic ALI mice. In LPS-induced fibroblasts, silencing of ZBTB16 suppressed the expression of inflammatory and fibrotic markers by inhibition of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2)-mediated glycolysis.
CONCLUSION: ZBTB16 promotes the transcription of glycolytic enzyme PFKFB2 to participate in fibrogenesis in septic lung injury. Our study may offer a potentially promising target for the treatment of fibrogenesis in septic lung injury.