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 rnas (circrnas) have crucial roles in various diseases; however, the mechanisms of action underlying circrnas in the occurrence and development of diabetic nephropathy (dn) remains largely unknown. The present study investigated the differentially expressed circrnas in the dn mice kidney cortex using circrna sequencing and elucidated the role of circrnas in mesangial cells. it was revealed that 40 circrnas were unconventionally expressed, including 18 upregulated circrnas 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 (ecM)-associated protein synthesis mediated by knocking-down circrna_0000491. in conclusion, the present study investigated the circrna_0000491/mir-101b/TGFβri axis in ecM 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.

Circular RNA circ_0000712 regulates high glucose-induced apoptosis, inflammation, oxidative stress, and fibrosis in (DN) by targeting the miR-879-5p/SOX6 axis

“…Since the abnormal development of MCs was correlated with the pathological changes of DN, MCs have been widely utilized for DN research in vitro [23,24]. In current work, the upregulation of circ_0000712 in the db/db DN mice and HG-triggered MCs was verified, in agreement with the previous study [14]. Also, our data showed the stability of circ_0000712, suggesting the underlying diagnostic and prognostic biomarker for DN.…”

“…Similarly, Chen et al found that circLRP6 as a competing endogenous RNA (ceRNA) of miR-205 to boost HGtriggered MCs proliferation, oxidative stress, and inflammation in DN [13]. Of note, a prior study indicated that a novel circRNA, circ_0000712 was identified to be increased in kidney tissues and HG-inducted MCs [14]. To our knowledge, the precise role and underlying mechanism of circ_0000712 in DN remain largely unknown.…”

Circ-ACTR2 aggravates the high glucose-induced cell dysfunction of human renal mesangial cells through mediating the miR-205-5p/HMGA2 axis in diabetic nephropathy

“…CircRNA_010383 has been reported as a miR-135a sponge to increase the level of TRPC1 in regulating the high glucose (HG)-induced renal fibrosis in DN [ 11 ]. Circ_0000491 has exacerbated the accumulation of ECM in mesangial cells by inhibiting miR-101b to upregulate the TGFβRI expression [ 12 ].…”

Interactions among Long Non-Coding RNAs and microRNAs Influence Disease Phenotype in Diabetes and Diabetic Kidney Disease

“…Similarly, research on circular RNAs and their role in the health and disease of diabetic kidneys is gaining momentum as well. circRNA_15698, circLRP6, circACTR2, circHIPK3 and circ_0000491 are associated with renal inflammation and fibrosis whereas circRNA_010383 is reno-protective [ 135 , 136 , 137 , 138 , 139 , 140 ]. Therefore, better understanding of the role of these regulatory circular RNAs in the physiology of diverse kidney cell types is needed.…”