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Resveratrol Ameliorates Fibrosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease via the Autophagy-Lysosome Pathway.

Abstract
Interstitial lung disease associated with rheumatoid arthritis (RA-ILD) can lead to interstitial fibrosis and even lung failure as a complication of rheumatoid arthritis (RA), and there is currently no effective treatment and related basic research. Studies have found that resveratrol (Res) can improve the progression of RA by regulating autophagy, and increasing evidence supports the connection between autophagy and common interstitial lung disease (ILD). We explored changes in autophagy levels in fibrotic lungs in RA-ILD and found that the level of autophagy is enhanced in the early stage but inhibited in the late stage. However, resveratrol treatment improved the level of autophagy and reversed the inhibition of autophagy, and attenuated fibrosis. We created corresponding cell models that exhibited the same phenotypic changes as animal models; under the effect of resveratrol, the level of fibrosis changed accordingly, and the fusion process of lysosomes and autophagosomes in autophagy was liberated from the inhibition state. Resveratrol effects were reversed by the addition of the late autophagy inhibitor chloroquine. These results suggest that resveratrol attenuates pulmonary fibrosis, increases autophagic flux, and modulates the autophagy-lysosome pathway, and particularly it may work by improving the formation of autophagic lysosomes, which may be an effective treatment for induced RA-ILD.
AuthorsLanxin Bao, Jing Ye, Nannan Liu, Yubao Shao, Wenhao Li, Xuefei Fan, Dahai Zhao, Hongzhi Wang, Xiaoyu Chen
JournalMolecules (Basel, Switzerland) (Molecules) Vol. 27 Issue 23 (Dec 02 2022) ISSN: 1420-3049 [Electronic] Switzerland
PMID36500562 (Publication Type: Journal Article)
Chemical References
  • Resveratrol
Topics
  • Animals
  • Resveratrol (pharmacology)
  • Lung Diseases, Interstitial (etiology, complications)
  • Arthritis, Rheumatoid (complications, drug therapy)
  • Fibrosis
  • Pulmonary Fibrosis (drug therapy, etiology)
  • Autophagy

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