NDLI: Metformin attenuates chronic lung allograft dysfunction: evidence in rat models

Content Provider	Springer Nature : BioMed Central
Author	Tian, Dong Zheng, Xiangyun Tang, Hongtao Huang, Heng Wang, Junjie Xu, Lin Li, Caihan Yan, Haoji Yu, Ruixuan Nan, Jinzhu Liu, Menggen Guo, Xiaoguang Jian, Shunhai Wang, Tao Deng, Senyi Pu, Qiang Liu, Lunxu
Abstract	Background Chronic lung allograft dysfunction (CLAD) directly causes an abysmal long-term prognosis after lung transplantation (LTx), but effective and safe drugs are not available. Metformin exhibits high therapeutic potential due to its antifibrotic and immunomodulatory effects; however, it is unclear whether metformin exerts a therapeutic effect in CLAD. We sought to investigate the effect of metformin on CLAD based on rat models. Methods Allogeneic LTx rats were treated with Cyclosporin A (CsA) in the first week, followed by metformin, CsA, or vehicle treatment. Syngeneic LTx rats received only vehicles. All rats were sacrificed on post-transplant week 4. Pathology of lung graft, spleen, and thymus, extent of lung fibrosis, activity of profibrotic cytokines and signaling pathway, adaptive immunity, and AMPK activity were then studied. Results Allogeneic recipients without maintenance CsA treatment manifested CLAD pathological characteristics, but these changes were not observed in rats treated with metformin. For the antifibrotic effect, metformin suppressed the fibrosis extent and profibrotic cytokine expression in lung grafts. Regarding immunomodulatory effect, metformin reduced T- and B-cell infiltration in lung grafts, spleen and thymus weights, the T- and B-cell zone areas in the spleen, and the thymic medullary area. In addition, metformin activated AMPK in lung allografts and in α-SMA+ cells and T cells in the lung grafts. Conclusions Metformin attenuates CLAD in rat models, which could be attributed to the antifibrotic and immunomodulatory effects. AMPK activation suggests the potential molecular mechanism. Our study provides an experimental rationale for further clinical trials.
Related Links	https://respiratory-research.biomedcentral.com/counter/pdf/10.1186/s12931-023-02492-5.pdf
Ending Page	15
Page Count	15
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12931-023-02492-5
Journal	Respiratory Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2023-07-29
Access Restriction	Open
Subject Keyword	Pneumology Respiratory System Metformin Lung transplantation Chronic lung allograft rejection Chronic lung allograft dysfunction AMP-activated kinase Pneumology/Respiratory System
Content Type	Text
Resource Type	Article
Subject	Pulmonary and Respiratory Medicine
Journal Impact Factor	4.7/2023
5-Year Journal Impact Factor	5.3/2023

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