期刊
ONCOTARGET
卷 8, 期 10, 页码 16109-16121出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.14884
关键词
senescence; epithelial-mesenchymal transition; short-term caloric restriction; caloric restriction mimetics; AMPK/mTOR signaling; Gerotarget
资金
- National Basic Research Program of China [2013CB530800]
- National Key Technology RD Program [2015BAI12B06, 2013BAI09B05]
- National Natural Science Foundation of China [81070267, 81401160]
- 863 Program [2012AA02A512]
Renal fibrosis contributes to declining renal function in the elderly. What is unclear however, is whether epithelial-mesenchymal transition (EMT) contributes to this age-related renal fibrosis. Here, we analyzed indicators of EMT during kidney aging and investigated the protective effects and mechanisms of short-term regimens of caloric restriction (CR) or caloric restriction mimetics (CRMs), including resveratrol and metformin. High glucose was used to induce premature senescence and EMT in human primary proximal tubular cells (PTCs) in vitro. To test the role of AMPKmTOR signaling, siRNA was used to deplete AMPK. Cellular senescence and AMPKmTOR signaling markers associated with EMT were detected. CR or CRMs treatment alleviated age-related EMT in aging kidneys, which was accompanied by activation of AMPK-mTOR signaling. High glucose induced premature senescence and EMT in PTCs in vitro, which was accompanied by down-regulation of AMPK/mTOR signaling. CRMs alleviated high glucose-induced senescence and EMT via stimulation of AMPK/ mTOR signaling. Activation of AMPK/mTOR signaling protected PTCs from high glucose-induced EMT and cellular senescence. Short-term regimens of CR and CRMs alleviated age-related EMT via AMPK-mTOR signaling, suggesting a potential approach to reducing renal fibrosis during aging.
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