Ministry of Education Key Laboratory of Molecular and Cellular Biology, Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, College of Life Sciences, Hebei Normal University, Hebei Research Center of the Basic Discipline of Cell Biology, Hebei Collaborative Innovation Center for Eco-Environment, Shijiazhuang, Hebei, China.
Department of Laboratory, Hebei Provincial People's Hospital, Shijiazhuang, Hebei, China.
Front Endocrinol (Lausanne). 2024 May 24;15:1379521. doi: 10.3389/fendo.2024.1379521. eCollection 2024.
At present, pulmonary fibrosis (PF) is a prevalent and irreversible lung disease with limited treatment options, and idiopathic pulmonary fibrosis (IPF) is one of its most common forms. Recent research has highlighted PF as a metabolic-related disease, including dysregulated iron, mitochondria, lipid, and glucose homeostasis. Systematic reports on the regulatory roles of glucose metabolism in PF are rare. This study explores the intricate relationships and signaling pathways between glucose metabolic processes and PF, delving into how key factors involved in glucose metabolism regulate PF progression, and the interplay between them. Specifically, we examined various enzymes, such as hexokinase (HK), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), pyruvate kinase (PK), and lactate dehydrogenase (LDH), illustrating their regulatory roles in PF. It highlights the significance of lactate, alongside the role of pyruvate dehydrogenase kinase (PDK) and glucose transporters (GLUTs) in modulating pulmonary fibrosis and glucose metabolism. Additionally, critical regulatory factors such as transforming growth factor-beta (TGF-β), interleukin-1 beta (IL-1β), and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were discussed, demonstrating their impact on both PF and glucose metabolic pathways. It underscores the pivotal role of AMP-activated protein kinase (AMPK) in this interplay, drawing connections between diabetes mellitus, insulin, insulin-like growth factors, and peroxisome proliferator-activated receptor gamma (PPARγ) with PF. This study emphasizes the role of key enzymes, regulators, and glucose transporters in fibrogenesis, suggesting the potential of targeting glucose metabolism for the clinical diagnosis and treatment of PF, and proposing new promising avenues for future research and therapeutic development.
目前，肺纤维化（PF）是一种流行且不可逆转的肺部疾病，治疗方法有限，特发性肺纤维化（IPF）是其最常见的形式之一。最近的研究强调 PF 是一种与代谢相关的疾病，包括铁、线粒体、脂质和葡萄糖稳态的失调。关于葡萄糖代谢在 PF 中调节作用的系统报告很少。本研究探讨了葡萄糖代谢过程与 PF 之间的复杂关系和信号通路，深入研究了参与葡萄糖代谢的关键因素如何调节 PF 的进展，以及它们之间的相互作用。具体来说，我们研究了各种酶，如己糖激酶（HK）、6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶 3（PFKFB3）、丙酮酸激酶（PK）和乳酸脱氢酶（LDH），阐明了它们在 PF 中的调节作用。它强调了乳酸的重要性，以及丙酮酸脱氢酶激酶（PDK）和葡萄糖转运蛋白（GLUTs）在调节肺纤维化和葡萄糖代谢中的作用。此外，还讨论了转化生长因子-β（TGF-β）、白细胞介素-1β（IL-1β）和缺氧诱导因子 1 亚基α（HIF-1α）等关键调节因子，表明它们对 PF 和葡萄糖代谢途径都有影响。它强调了 AMP 激活的蛋白激酶（AMPK）在这种相互作用中的关键作用，将糖尿病、胰岛素、胰岛素样生长因子和过氧化物酶体增殖物激活受体γ（PPARγ）与 PF 联系起来。本研究强调了关键酶、调节剂和葡萄糖转运体在纤维化中的作用，表明针对葡萄糖代谢进行临床诊断和治疗 PF 的潜力，并为未来的研究和治疗发展提出了新的有前途的途径。
