Dihydromyricetin Alleviates Pulmonary Fibrosis by Regulating Abnormal Fibroblasts Through the STAT3/p-STAT3/GLUT1 Signaling Pathway

Zhen Li; Jing Geng; Bingbing Xie; Jiarui He; Jing Wang; Liang Peng; Yinan Hu; Huaping Dai; Chen Wang

doi:10.3389/fphar.2022.834604

Dihydromyricetin Alleviates Pulmonary Fibrosis by Regulating Abnormal Fibroblasts Through the STAT3/p-STAT3/GLUT1 Signaling Pathway

Front Pharmacol. 2022 Mar 14:13:834604. doi: 10.3389/fphar.2022.834604. eCollection 2022.

Authors

Zhen Li¹, Jing Geng¹, Bingbing Xie¹, Jiarui He¹, Jing Wang², Liang Peng³, Yinan Hu¹, Huaping Dai¹, Chen Wang¹

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
² State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
³ Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with a poor prognosis. Although dihydromyricetin (DHM), extracted from vine tea and other Ampelopsis species, has been proven to have anti-inflammatory and antioxidant functions, the effects of DHM on IPF remain unclear. Methods: The effects of DHM on the differentiation, migration, proliferation, and respiratory functions of primary mouse lung fibroblasts (PMLFs) and primary human lung fibroblasts (PHLFs) were detected by western blotting, the Transwell assay, EdU staining, and the Mito Stress test. Then, the impacts of DHM on bleomycin (BLM)-induced pulmonary fibrosis were evaluated by pathological staining, western blotting, and coimmunofluorescence staining. The signaling pathway influenced by DHM was also investigated. Results: DHM could regulate the differentiation of fibroblasts to myofibroblasts and suppress the abnormal migration, proliferation, and respiratory functions of myofibroblasts induced by TGF-β1 or myofibroblasts from IPF patients. DHM could also alleviate pulmonary fibrosis induced by BLM. All these effects were achieved by regulating the STAT3/p-STAT3/GLUT1 signaling pathway. Conclusion: DHM could regulate the abnormal functions of myofibroblasts induced by TGF-β1 and myofibroblasts from IPF patients and alleviate pulmonary fibrosis induced by BLM; thus, DHM might be a candidate medicinal treatment for IPF.

Keywords: GLUT1; dihydromyricetin; fibroblast; glucose metabolism; idiopathic pulmonary fibrosis; myofibroblast.