Fluvoxamine alleviates bleomycin-induced lung fibrosis via regulating the cGAS-STING pathway. (January 2023)

• Record Type: Journal Article
• Authors: Xie, Xiaohua; Wu, Xiaofeng; Zhao, Dongsheng; Liu, Ying; Du, Qiyue; Li, Yitian; Xu, Yaping; Li, Yuhang; Qiu, Yan; Yang, Yungang
• Is Part Of: Pharmacological research. Volume 187(2023)
• Publication Date: 2023-01
• Subjects: Idiopathic pulmonary fibrosis (IPF) -- Cyclic GMP-AMP synthase (cGAS) -- Stimulator of interferon genes (STING) -- Fluvoxamine -- Bleomycin; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106577
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9–5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-β1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF. Graphical Abstract: ga1