Open AccessCaloric restriction alleviates aging-related fibrosis of kidney through downregulation of miR-21 in extracellular vesicles
Author(s) -
Jin-Rui Liu,
Guangyan Cai,
Yuping Ning,
Jingchao Wang,
Yang Lv,
Junming Guo,
Bo Fu,
Quan Hong,
Xuefeng Sun,
Xiangmei Chen
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.103591
Subject(s) - downregulation and upregulation , fibrosis , glomerulosclerosis , endocrinology , senescence , extracellular vesicle , calorie restriction , medicine , kidney , epithelial–mesenchymal transition , peroxisome proliferator activated receptor , biology , cancer research , microrna , receptor , microvesicles , biochemistry , proteinuria , gene
Glomerulosclerosis and renal interstitial fibrosis occur with the aging kidney. In this study, we examined the expression of miR-21, peroxisome proliferator-activated receptor(PPARα), hypoxia-inducible factor(HIF-1α) in the kidney of 3-month-old rats fed ad libitum (YAL), 24-month-old rats fed ad libitum (OAL) and 24-month-old rats subjected to a 70% calorie-restricted diet for 8 months (OCR). We found long-term caloric restriction (CR) ameliorated aging and aging-related fibrosis. CR ameliorated the increment of miR-21 and HIF-1α, as well as the decrement of PPARα in old ad libitum group. Human proximal tubular cells (HPTCs) presented phenotypes of senescence and epithelial to mesenchymal transition (EMT) under high-glucose conditions, in which senescence occurred earlier than EMT. Senescent cells secreted extracellular vesicles (EVs) which contained miR-21 into the recipient cells. Inhibiting miR-21 of donor cells prevented the occurrence of EMT in recipient cells. In addition, miR-21 induced EMT through targeting PPARα protein and consequently enhancing HIF-1α expression, although other pathways cannot be ruled out. These findings demonstrated that miR-21-containing EVs derived from the senescent cells could facilitate EMT of HPTCs via PPARα-HIF-1α signaling pathway. Long-term caloric restriction and caloric restriction mimetics alleviated aging-related-fibrosis of kidney through downregulation of miR-21.