Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, South Korea.
Medical Device Usability Test Center, Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
PLoS One. 2023 Feb 16;18(2):e0281640. doi: 10.1371/journal.pone.0281640. eCollection 2023.
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.
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-β1) 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.
Glycolysis of nasal fibroblasts stimulated with TGF-B1 was upregulated along with glycolytic enzymes. Hypoxia-inducing factor (HIF)-1α was a high-level regulator of glycolysis, and increased HIF-1α expression promoted glycolysis of nasal fibroblasts, and inhibition of HIF-1α down-regulated myofibroblasts differentiation and ECM production.
This study suggests that inhibition of the glycolytic enzyme and HIF-1α in nasal fibroblasts regulates myofibroblast differentiation and ECM generation associated with nasal mucosa remodeling.
糖酵解重编程是慢性炎症性疾病的一个关键特征。肌成纤维细胞产生的细胞外基质（ECM）在慢性鼻-鼻窦炎（CRS）的鼻黏膜组织重塑中起着重要作用。本研究旨在确定糖酵解重编程是否有助于鼻成纤维细胞中的肌成纤维细胞分化和 ECM 产生。
从 CRS 患者的鼻黏膜中分离出原代鼻成纤维细胞。通过测量 TGF-β1 处理前后鼻成纤维细胞的细胞外酸化率和耗氧量来评估糖酵解重编程。通过实时聚合酶链反应、western blot 和免疫细胞化学染色来测量糖酵解酶和 ECM 成分的表达。使用健康供体和 CRS 患者鼻黏膜的全 RNA 测序数据进行基因集富集分析。
TGF-B1 刺激的鼻成纤维细胞的糖酵解被上调，同时糖酵解酶也被上调。缺氧诱导因子（HIF）-1α是糖酵解的高水平调节剂，增加 HIF-1α 的表达促进了鼻成纤维细胞的糖酵解，而抑制 HIF-1α 则下调了肌成纤维细胞的分化和 ECM 的产生。
本研究表明，抑制鼻成纤维细胞中的糖酵解酶和 HIF-1α 可调节与鼻黏膜重塑相关的肌成纤维细胞分化和 ECM 生成。
