The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Metformin reverses established lung fibrosis in a bleomycin model
Open accessAbstract
Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in a number of organs, including the lungs1. Cellular metabolism regulates tissue repair and remodelling responses to injury2–4. AMPK is a critical sensor of cellular bioenergetics and controls the switch from anabolic to catabolic metabolism5. However, the role of AMPK in fibrosis is not well understood. Here, we demonstrate that in humans with idiopathic pulmonary fibrosis (IPF) and in an experimental mouse model of lung fibrosis, AMPK activity is lower in fibrotic regions associated with metabolically active and apoptosis-resistant myofibroblasts. Pharmacological activation of AMPK in myofibroblasts from lungs of humans with IPF display lower fibrotic activity, along with enhanced mitochondrial biogenesis and normalization of sensitivity to apoptosis. In a bleomycin model of lung fibrosis in mice, metformin therapeutically accelerates the resolution of well-established fibrosis in an AMPK-dependent manner. These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes, and support a role for metformin (or other AMPK activators) to reverse established fibrosis by facilitating deactivation and apoptosis of myofibroblasts. Metformin reverses established lung fibrosis in a bleomycin model in mice.
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Cites
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Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600
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Cited by
Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus
Foretz, M., Guigas, B., & Viollet, B. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0242-2 · Cited by 686
Cellular Senescence as a Mechanism and Target in Chronic Lung Diseases
Barnes, P. J., Baker, J., & Donnelly, L. E. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201810-1975tr · Cited by 555
Targeting metabolic dysregulation for fibrosis therapy
Zhao, X., Kwan, J. Y. Y., Yip, K., Liu, P. P., & Liu, F.-F. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0040-5 · Cited by 513
Metabolism of tissue macrophages in homeostasis and pathology
Wculek, S. K., Dunphy, G., Heras-Murillo, I., Mastrangelo, A., & Sancho, D. (2022) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00791-9 · Cited by 501
Inhibition of ferroptosis and iron accumulation alleviates pulmonary fibrosis in a bleomycin model
Pei, Z., Qin, Y., Fu, X., Yang, F., Huo, F., Liang, X., Wang, S., Cui, H., Lin, P., Zhou, G., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102509 · Cited by 269
Metadata
- Authors
- Rangarajan, S., Bone, N. B., Zmijewska, A. A., Jiang, S., Park, D. W., Bernard, K., Locy, M. L., Ravi, S., Deshane, J., Mannon, R. B., Abraham, E., Darley-Usmar, V., Thannickal, V. J., & Zmijewski, J. W.
- Venue
- Nature Medicine
- Published
- 2018-07-02
- Volume
- 24
- Issue
- 8
- Pages
- 1121-1127
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2809779343
- Cited by
- 560
- References
- 46
- FWCI
- 38.72
- Type
- journal article
- Language
- en
- Open access
- green
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- Rangarajan, S., Bone, N. B., Zmijewska, A. A., Jiang, S., Park, D. W., Bernard, K., Locy, M. L., Ravi, S., Deshane, J., Mannon, R. B., Abraham, E., Darley-Usmar, V., Thannickal, V. J., & Zmijewski, J. W. (2018). Metformin reverses established lung fibrosis in a bleomycin model. Nature Medicine. https://doi.org/10.1038/s41591-018-0087-6
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