A novel identified circular RNA, circ-0000491, aggravates the extracellular matrix of diabetic nephropathy glomerular mesangial cells through suppressing miR-101b by targeting TGFβRI

Abstract

Circular RNA s (circRNA s) have crucial roles in various diseases; however, the mechanisms of action underlying circRNA s in the occurrence and development of diabetic nephropathy (DN ) remains largely unknown. The present study investigated the differentially expressed circRNA s in the DN mice kidney cortex using circRNA sequencing and elucidated the role of circRNA s in mesangial cells. It was revealed that 40 circRNA s were unconventionally expressed, including 18 upregulated circRNA s and 22 downregulated circRNAs. Furthermore, circ-0000491 levels were significantly augmented in both DN mice and high glucose (HG, 30 mM)-induced mouse mesangial cells (MES13 cells). Knockdown of circ-0000491 significantly suppressed the increase of vimentin, fibronectin and α-smooth muscle actin, as well as collagen type I, III and IV, whilst reversing the decrease of E- cadherin in HG-induced MES13 cells. It was further revealed that circRNA _0000491 sponged miR- 101b and that miR- 101b directly targets TGFβRI . In addition, the expression levels of miR- 101b were negatively associated with the transcriptional level of circRNA _0000491 and miR- 101b inhibitors reversed the suppression of extracellular matrix (EC M)-associated protein synthesis mediated by knocking-down circRNA _0000491. In conclusion, the present study investigated the circRNA _0000491/miR- 101b/TGFβRI axis in EC M accumulation and fibrosis-associated protein expression levels of mesangial cells, which suggested that circRNA_0000491 may be beneficial for the development of an effective therapeutic target for DN .