tRF3-IleAAT reduced extracellular matrix synthesis in diabetic kidney disease mice by targeting ZNF281 and inhibiting ferroptosis.

It is well established that the synthesis of extracellular matrix (ECM) in mesangial cells is a major determinant of diabetic kidney disease (DKD). Elucidating the major players in ECM synthesis may be helpful to provide promising candidates for protecting against DKD progression. tRF3-IleAAT is a tRNA-derived fragment (tRF) produced by nucleases at tRNA-specific sites, which is differentially expressed in the sera of patients with diabetes mellitus and DKD. In this study we investigated the potential roles of tRFs in DKD. Db/db mice at 12 weeks were adapted as a DKD model. The mice displayed marked renal dysfunction accompanied by significantly reduced expression of tRF3-IleAAT and increased ferroptosis and ECM synthesis in the kidney tissues. The reduced expression of tRF3-IleAAT was also observed in high glucose-treated mouse glomerular mesangial cells. We administered ferrostatin-1 (1 mg/kg, once every two days, i.p.) to the mice from the age of 12 weeks for 8 weeks, and found that inhibition of the onset of ferroptosis significantly improved renal function, attenuated renal fibrosis and reduced collagen deposition. Overexpression of tRF3-IleAAT by a single injection of AAV carrying tRF3-IleAAT via caudal vein significantly inhibited ferroptosis and ECM synthesis in DKD model mice. Furthermore, we found that the expression of zinc finger protein 281 (ZNF281), a downstream target gene of tRF3-IleAAT, was significantly elevated in DKD models but negatively regulated by tRF3-IleAAT. In high glucose-treated mesangial cells, knockdown of ZNF281 exerted an inhibitory effect on ferroptosis and ECM synthesis. We demonstrated the targeted binding of tRF3-IleAAT to the 3'UTR of ZNF281. In conclusion, tRF3-IleAAT inhibits ferroptosis by targeting ZNF281, resulting in the mitigation of ECM synthesis in DKD models, suggesting that tRF3-IleAAT may be an attractive therapeutic target for DKD.

[Serum levels of IL-13 and TNF-alpha in children with Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To examine serum levels of interleukin-13 (IL-13) and tumor necrosis factor alpha (TNF-alpha) in children with Mycoplasma pneumoniae (MP) pneumonia. METHODS: Eighty children with MP pneumonia complicated by wheezing or without (n=40 each), 40 children with pneumonia from non-MP infection and 40 healthy children were enrolled. Serum levels of IL-13 and TNF-alpha were measured using ELISA. RESULTS: The serum levels of IL-13 and TNF-alpha in the MP pneumonia group were significantly higher than those in non-MP pneumonia group and the healthy control group (P<0.01). The children with MP pneumonia complicated by wheezing had increased serum levels of IL-13 (214.6 + or - 67.2 ng/L vs 189.6 + or - 52.1 ng/L; P<0.01) and TNF-alpha(0.55 + or - 0.13 ng/mL vs 0.42 + or - 0.16 ng/mL; P<0.01)compared with those without wheezing. CONCLUSIONS: The increase in serum levels of IL-13 and TNF-alpha may play important roles in the pathogenesis of MP pneumonia and wheezing attack in children.