Glycolytic reprogramming is involved in tissue remodeling on chronic rhinosinusitis

Abstract

Background Glycolytic reprogramming is a key feature of chronic inflammatory disease. Extracellular matrix (ECM) produced by myofibroblasts plays an important role in tissue remodeling of nasal mucosa in chronic rhinosinusitis (CRS). This study aimed to determine whether glycolytic reprogramming contributes to myofibroblast differentiation and ECM production in nasal fibroblasts. Methods Primary nasal fibroblasts were isolated from the nasal mucosa of patients with CRS. Glycolytic reprogramming was assessed by measuring the extracellular acidification and oxygen consumption rates in nasal fibroblast, with and without transforming growth factor beta 1 (TGF-beta 1) treatment. Expression of glycolytic enzymes and ECM components was measured by real-time polymerase chain reaction, western blotting, and immunocytochemical staining. Gene set enrichment analysis was performed using whole RNA-sequencing data of nasal mucosa of healthy donors and patients with CRS. Result Glycolysis of nasal fibroblasts stimulated with TGF-B1 was upregulated along with glycolytic enzymes. Hypoxia-inducing factor (HIF)-1 alpha was a high-level regulator of glycolysis, and increased HIF-1 alpha expression promoted glycolysis of nasal fibroblasts, and inhibition of HIF-1 alpha down-regulated myofibroblasts differentiation and ECM production. Conclusion This study suggests that inhibition of the glycolytic enzyme and HIF-1 alpha in nasal fibroblasts regulates myofibroblast differentiation and ECM generation associated with nasal mucosa remodeling.