Upregulation of circ-0069561 promotes diabetic kidney disease progression

Circular RNAs (circRNAs) are non-coding RNAs that play a critical role in disease etiology. But the role of circRNAs in diabetic kidney disease (DKD) remains unknown. We performed whole high-throughput RNA sequencing (RNA-seq) of kidney tissues from clinical DKD patients and controls. The top 10 up-regulated circular RNAs were selected by RT-PCR validation, and the findings showed a substantial increase in the expression level of circ-0069561. RT-PCR and fluorescent in situ hybridization (FISH) confirmed that circ-0069561 expression increased both renal tissues of type 2 diabetic mice and DKD patients, with a glomerulus-specific location. Circ-0069561 expression in kidney tissue was significantly correlated with UACR, glomerular lesions, arteriolar hyalinosis and arteriosclerosis. The expression level of circ-0069561 and plasma albumin (ALB) level were independent risk factors for macroalbuminuria. Circ-0069561 demonstrated a strong diagnostic value in major proteinuria, according to the ROC curves (area under the curve = 0.889). CircRNA-miRNA-mRNA network indicated that the pathophysiology of DKD may involve ferroptosis. Podocyte damage and ferroptosis caused by high glucose were attenuated by silencing circ-0069561, according to in vitro examinations. Together, the findings suggest that circ-0069561 may influence the progression of DKD by causing ferroptosis of podocytes. The findings of this study provide new insights into the cause and progression of DKD.