2. Academic Validation
  3. Fluvoxamine alleviates bleomycin-induced lung fibrosis via regulating the cGAS-STING pathway

Fluvoxamine alleviates bleomycin-induced lung fibrosis via regulating the cGAS-STING pathway

  • Pharmacol Res. 2022 Nov 23;106577. doi: 10.1016/j.phrs.2022.106577.
Xiaohua Xie 1,  Xiaofeng Wu 2,  Dongsheng Zhao 3,  Ying Liu 4,  Qiyue Du 4,  Yitian Li 5,  Yaping Xu 6,  Yuhang Li 7,  Yan Qiu 4,  Yungang Yang 8
Affiliations

Affiliations

  • 1 Department of Pediatrics, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China; Institute of Pediatrics, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China.
  • 2 Department of Pharmacy, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
  • 3 Department of Pharmacy, Quanzhou Medical College, China.
  • 4 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361102, China.
  • 5 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361102, China; Department of Clinical Pharmacy, The Third Hospital of Mianyang/Sichuan Mental Health Center, Mianyang, 621000, Sichuan, China.
  • 6 Institute of Respiratory Diseases Xiamen Medical College; Xiamen, Fujian, 361002, China; Key laboratory of functional and clinical translational medicine, Fujian province university, Xiamen Medical College; Xiamen, Fujian, 361002, China.
  • 7 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, China; Xiamen Institute of Rare-earth Materials, Haixi Institutes, Chinese Academy of Sciences, Fujian, 361005, China. Electronic address: [email protected].
  • 8 Department of Pediatrics, The First Affiliated Hospital of Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China; Institute of Pediatrics, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China. Electronic address: [email protected].
PMID: 36435270 DOI: 10.1016/j.phrs.2022.106577
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 10mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.

Keywords

Fluvoxamine; Idiopathic pulmonary fibrosis (IPF); bleomycin; cyclic GMP-AMP synthase (cGAS); stimulator of interferon genes (STING).

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