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.