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Aim to investigate the mechanism of AMPK-FoxO3a pathway mediated autophagy during fibroblast-myofibroblast differentiation in PF. Methods we used BLM to induce PF in SD rats, and treatment with an AMPK activator(metformin) in model group. The pathological change and collagen deposition of lung tissue was observed by H&E and Masson staining. Meanwhile, we detected related proteins by immunohistochemistry and western blot. Meanwhile, human lung fibroblast were stimulated with TGF-β1, and the cells were treated with AMPK activator(Metformin and AICAR), and activator and inhibitor of autophagy. Furthermore, the FoxO3a small RNA was used to interference cells. The related proteins and autophagy were detected by western blot. Results In vivo, AMPK could reduce the destruction of alveolar structure and collagen deposition. In addition, AMPK could increase the expression of FoxO3a and autophagy level. In vitro, the protect effect of AMPK was abolished when FoxO3a was silenced by small RNA. Meanwhile, activation of autophagy by starvation and rapamycin could decrease TGF-β1 induced fibroblast differentiation. However, when autophagy was inhibited by 3-MA or chloroquine, the TGF-β1 induced FMD was aggravated again under the pre-treatment with metformin. Conclusion AMPK-FoxO3a pathway could attenuate FMD by increasing autophagy in PF Support or Funding Information National Natural Science Foundation of China No. 81473267, 81274172. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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