Prednisolone suppresses adriamycin-induced vascular smooth muscle cell senescence and inflammatory response via the SIRT1-AMPK signaling pathway

• Published in: PloS one Vol. 15; no. 9; p. e0239976
• Main Authors: Sung, Jin Young, Kim, Seul Gi, Kim, Jae-Ryong, Choi, Hyoung Chul
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-09-2020; Public Library of Science (PLoS)
• Subjects: Age related diseases; Aging; AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Antibodies; Aorta - drug effects; Aorta - metabolism; Atherosclerosis; Biology and Life Sciences; Cell culture; Cellular Senescence - drug effects; Cellular signal transduction; Complications and side effects; Down-Regulation - drug effects; Doxorubicin; Doxorubicin - pharmacology; Drug therapy; Health aspects; Inflammation; Inflammatory response; Kinases; Male; Medical schools; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Morphology; Muscle cells; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscles; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB protein; Pharmacology; Phenotypes; Phosphorylation; Phosphorylation - drug effects; Physiological aspects; Prednisolone; Prednisolone - pharmacology; Proteins; Rats; Rats, Sprague-Dawley; Research and analysis methods; RNA Interference; RNA, Small Interfering - metabolism; Senescence; Signal transduction; Signal Transduction - drug effects; Signaling; siRNA; SIRT1 protein; Sirtuin 1 - antagonists & inhibitors; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Smooth muscle; Tumor Suppressor Protein p53 - metabolism; Vascular diseases; Western blotting; South Korea; Delaware; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0239976

Cellular senescence is associated with inflammation and the senescence-associated secretory phenotype (SASP) of secreted proteins. Vascular smooth muscle cell (VSMC) expressing the SASP contributes to chronic vascular inflammation, loss of vascular function, and the developments of age-related diseases. Although VSMC senescence is well recognized, the mechanism of VSMC senescence and inflammation has not been established. In this study, we aimed to determine whether prednisolone (PD) attenuates adriamycin (ADR)-induced VSMC senescence and inflammation through the SIRT1-AMPK signaling pathway. We found that PD inhibited ADR-induced VSMC senescence and inflammation response by decreasing p-NF-κB expression through the SIRT1-AMPK signaling pathway. In addition, Western blotting revealed PD not only increased SIRT1 expression but also increased the phosphorylation of AMPK at Ser485 in ADR-treated VSMC. Furthermore, siRNA-mediated downregulation or pharmacological inhibitions of SIRT1 or AMPK significantly augmented ADR-induced inflammatory response and senescence in VSMC despite PD treatment. In contrast, the overexpression of SIRT1 or constitutively active AMPKα (CA-AMPKα) attenuated cellular senescence and p-NF-κB expression. Taken together, the inhibition of p-NF-κB by PD through the SIRT1 and p-AMPK (Ser485) pathway suppressed VSMC senescence and inflammation. Collectively, our results suggest that anti-aging effects of PD are caused by reduced VSMC senescence and inflammation due to reciprocal regulation of the SIRT1/p-AMPK (Ser485) signaling pathway.