MicroRNA-21: A Critical Pathogenic Factor of Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN), one of the most common and intractable microvascular complications of diabetes, is the main cause of terminal renal disease globally. MicroRNA-21 (miR-21) is a kind of miRNA early identified in human circulation and tissues. Mounting studies have demonstrated that miR-21 plays an important role in the development and progression of DN. This collaborative review aimed to present a first attempt to capture the current evidence on the relationship between miR-21 and DN. After a systematic search, 29 relevant studies were included for comprehensively and thoroughly reviewing. All these eligible studies reported that miR-21 was up-regulated in DN, whether in serum or renal tissues of human or animal models. MiR-21 exhibited its pathogenic roles in DN by forming a complex network with targeted genes (e.g. MMP-9, Smad7, TIMP3, Cdk6, FOXO1, IMP3, and MMP2) and the signaling cascades (e.g. Akt/TORC1 signaling axis, TGF-β/NF-κB signaling pathways, TGF-β/SMAD pathway, CADM1/STAT3 signaling, and AGE-RAGE regulatory cascade), which resulted in epithelial-to-mesenchymal transition, extracellular matrix deposition, cytoskeletal remodeling, inflammation, and fibrosis. This review highlights that miR-21 is a pivotal pathogenic factor in the development of DN. It may serve as an attractive potential diagnostic, prognostic, and predictive biomarker for DN in clinical practice after further confirmation of the clinicopathological features and molecular mechanisms of miR-21-mediated DN.

Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes

“…In particular, miR21 is induced by ROS [ 96 ] and plays a role in both PI3K-Akt and HIF-1α signaling activation [ 97 ]. Interestingly, miR21 has also been implicated in diabetes development and ROS-mediated damage [ 98 ] as well as DKD [ 99 , 100 ]. Together with the observation that PI3K and Akt signaling is altered by hyperglycemia [ 101 ], these findings suggest the involvement of a miR21-PI3K-Akt axis in the redox regulation of HIF in diabetic complications.…”

Editorial: Advances in the research of diabetic nephropathy, volume II

“…MicroRNA-21 is upregulated in the plasma, urine, and kidney tissues of patients with diabetic nephropathy and is anticipated to be a biomarker predicting the progression of diabetic kidney disease (8). Therefore, microRNA-21 plays an important role in the development and progression of DN (8). Liu et al reviewed the progress of microRNA-21 in the pathogenesis of diabetic nephropathy (8).…”

“…Therefore, microRNA-21 plays an important role in the development and progression of DN (8). Liu et al reviewed the progress of microRNA-21 in the pathogenesis of diabetic nephropathy (8). MicroRNA-21 exhibited its pathogenic roles in DN by forming a complex network with targeted genes such as MMP-9, Smad7, and TIMP3 and signaling cascades such as the Akt/TORC1 signaling axis, TGF-b/NF-kB signaling pathways, TGF-b/SMAD pathway, CADM1/STAT3 signaling, and AGE-RAGE regulatory cascade.…”

“…Thus, these results partly provide a clue to resolve the mechanism by which PKM2 activators improve renal function. MicroRNA-21 regulates various biological functions, such as proliferation, differentiation, migration, and apoptosis ( 8 ). MicroRNA-21 is upregulated in the plasma, urine, and kidney tissues of patients with diabetic nephropathy and is anticipated to be a biomarker predicting the progression of diabetic kidney disease ( 8 ).…”

“…MicroRNA-21 regulates various biological functions, such as proliferation, differentiation, migration, and apoptosis ( 8 ). MicroRNA-21 is upregulated in the plasma, urine, and kidney tissues of patients with diabetic nephropathy and is anticipated to be a biomarker predicting the progression of diabetic kidney disease ( 8 ). Therefore, microRNA-21 plays an important role in the development and progression of DN ( 8 ).…”