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Ginsenoside Rb2 suppresses cellular senescence of human dermal fibroblasts by inducing autophagy

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Author(s)
Kyeong Eun YangSoo-Bin NamMinsu JangJunsoo ParkGa-Eun LeeYong-Yeon ChoByeong-Churl JangCheol-Jung LeeJong-Soon Choi
Keimyung Author(s)
Jang, Byeong Churl
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
J Ginseng Res
Issued Date
2023
Volume
47
Issue
2
Keyword
AutophagyDRAM2Rb2Senescence
Abstract
Background:
Ginsenoside Rb2, a major active component of Panax ginseng, has various physiological activities, including anticancer and anti-inflammatory effects. However, the mechanisms underlying the rejuvenation effect of Rb2 in human skin cells have not been elucidated.

Methods:
We performed a senescence-associated β-galactosidase staining assay to confirm cellular senescence in human dermal fibroblasts (HDFs). The regulatory effects of Rb2 on autophagy were evaluated by analyzing the expression of autophagy marker proteins, such as microtubule-associated protein 1A/1B-light chain (LC) 3 and p62, using immunoblotting. Autophagosome and autolysosome formation was monitored using transmission electron microscopy. Autophagic flux was analyzed using tandem-labeled GFP-RFP-LC3, and lysosomal function was assessed with Lysotracker. We performed RNA sequencing to identify potential target genes related to HDF rejuvenation mediated by Rb2. To verify the functions of the target genes, we silenced them using shRNAs.

Results:
Rb2 decreased β-galactosidase activity and altered the expression of cell cycle regulatory proteins in senescent HDFs. Rb2 markedly induced the conversion of LC3-Ⅰ to LC3-Ⅱ and LC3 puncta. Moreover, Rb2 increased lysosomal function and red puncta in tandem-labeled GFP-RFP-LC3, which indicate that Rb2 promoted autophagic flux. RNA sequencing data showed that the expression of DNA damage-regulated autophagy modulator 2 (DRAM2) was induced by Rb2. In autophagy signaling, Rb2 activated the AMPK-ULK1 pathway and inactivated mTOR. DRAM2 knockdown inhibited autophagy and Rb2-restored cellular senescence.

Conclusion:
Rb2 reverses cellular senescence by activating autophagy via the AMPK-mTOR pathway and induction of DRAM2, suggesting that Rb2 might have potential value as an antiaging agent.
Keimyung Author(s)(Kor)
장병철
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1226-8453
Source
https://www.sciencedirect.com/science/article/pii/S1226845322001506?via%3Dihub
DOI
10.1016/j.jgr.2022.11.004
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44992
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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