Albendazole ameliorates aerobic glycolysis in myofibroblasts to reverse pulmonary fibrosis

作者：Chenxi Zeng, Huihui Yue, Congjian Wang, Xuetao Ju, Tianlai Wang, Xiangning Fu, Qing Zhou, Huilan Zhang, Long He, Jun Yu, Yi Wang · 发表于：Research Square · 年份：2023 · DOI：10.21203/rs.3.rs-3690679/v1 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Medical Imaging and Pathology Studies、Pulmonary Hypertension Research and Treatments

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disorder for which effective treatments remain limited. Recent investigations revealed a potential link between altered glucose metabolism and the activation of fibroblasts, the key cells responsible for generating and depositing extracellular matrix proteins within the lung interstitium during IPF development. Method In this study, we aimed to investigate the potential therapeutic impact of albendazole on fibroblast to myofibroblast transition in IPF. We assess albendazole ‘s effectiveness in attenuating the activation of fibroblasts. We focused on elucidating the mechanism underlying albendazole's impact on TGF-β1-induced aerobic glycolysis in both lung tissues and fibroblasts obtained from patients with IPF and other lung fibrosis types. Furthermore, the antifibrotic effects of oral administration of albendazole were investigated in mouse models of pulmonary fibrosis induced by BLM or SiO2. Human precision-cut lung slices were employed to evaluate the impact of albendazole following TGF-β1 stimulation. Result In this work, we demonstrated that albendazole, a first-line broad-spectrum anthelmintic drug, effectively attenuated fibroblast to myofibroblast transition through alleviating TGF-β1-induced aerobic glycolysis dependent on the LRRN3/PFKFB3 signaling pathway. Additionally, LRRN3 expression was downregulated in both lung tissues and fibroblasts from patients with IPF and other types of...