Effect of tRF-003634 on podocyte apoptosis in mice with adriamycin nephropathy and related mechanism

Objective To explore the effect of tRF-003634 (tRNA-derived fragment 003634) on podocyte apoptosis in mice with adriamycin nephropathy and related mechanism. Methods ①A model of adriamycin (10 mg/kg) nephropathy was established using BALB/c mice. 20 BALB/c mice were divided randomly into four groups (n=5): a control group, an ADR group, an ADR+tRF-003634 agomir group and an ADR+tRF-003634 NC group. Their serum biochemical indexes were detected, and the pathological changes in the kidneys were evaluated by HE and PAS staining. The expression of tRF-003634 in each group was detected by real-time PCR. The expression of caspase3, cleaved caspase3 and p53 was detected by Western blot. ②Adriamycin (1 mg/L) was used to induce podocyte apoptosis in vitro. According to different intervention factors, podocytes were divided into four groups: a control group, an ADR group, an ADR+tRF-003634 mimics group and an ADR+tRF-003634 NC group. The expression of tRF-003634 was detected by real-time PCR. The relative expression of caspase3, cleaved caspase3 and p53 in podocytes was examined by Western blot. ③Podocytes were divided into four groups: a control group, an ADR group, an ADR+SB203580 group and a SB203580 group. The expression of p-p38MAPK and p-Hsp27 was measured by Western blot, and the expression of tRF-003634 was detected by real-time PCR. Results ①Compared with the control group, the ADR group showed significantly increased pathological changes, as well as decreases in the expression of tRF-003634 and increases in the expression of cleaved caspase3 and p53 (P<0.05). Compared with the ADR group, mice in the ADR+tRF-003634 agomir group presented significantly reduced 24 h urine protein and serum urea nitrogen (P<0.05), with alleviated pathological changes, as well as increase in the expression of tRF-003634 decreases in the expression of cleaved caspase3 and p53 (P<0.05). ②Compared with the control group, the ADR group presented significant decreases in tRF-003634 expression, and increases in the levels of cleaved caspase3 and p53 (P<0.05). Compared with the ADR group, the tRF-003634 mimics group showed remarkably increased expression of tRF-003634 (P<0.05), and decreased expression of cleaved caspase3 and p53 (P<0.05). ③Compared with the control group, the expression of p-p38MAPK and p-Hsp27 in the ADR group was up-regulated, and the expression of tRF-003634 was down-regulated (P<0.05). Compared with the ADR group, the expression of p-p38MAPK and p-Hsp27 in the ADR+SB203580 group significantly decreased, and the expression of tRF-003634 increased (P<0.05). Conclusions tRF-003634 can inhibit the apoptosis of podocytes and alleviate renal pathological damage induced by adriamycin. tRF-003634 may act as a downstream effector molecule of MAPK pathway to improve podocyte apoptosis, providing new thoughts for the diagnosis and treatment of chronic renal disease.