Table 1.
Examples of certain micro RNAs (miRNAs) implicated in diabetes.
| miRNA | Cell/Tissue Type(s) | Reported Function(s) | Disease Model(s) |
|---|---|---|---|
| miR-192 * | • Mouse mesangial cells • Human proximal tubule cells and kidneys • Rat tubular epithelial cells • Human podocytes |
• Elevated expressions associated with increased Col1a2 expressions; targets SIP1 [108] • Loss of miR-192 expression is associated with increased fibrosis and decreased estimated GFR [111] • Decreased in the diabetic kidney, targets ZEB2, and does not affect extracellular matrix (ECM) protein expressions [112] • Increased in high glucose and diabetic conditions [109,110,142] • Can regulate other transcription factors and miRNAs [109,110] |
• DN [108,109,110,111,112,142] |
| miR-215 | • Proximal tubular cells • Rat mesangial cells • Human podocytes |
• Decreased in the diabetic kidney • Ectopic expression of miR-215 increases E-cadherin levels by repressing ZEB2 translation |
• DN [112] |
| miR-377 | • Human and mouse mesangial cells • Mice kidney tissues |
• Up-regulated in hyperglycemic and diabetic conditions • Can indirectly lead to increased fibronectin protein production |
• DN [113] |
| miR-21 | • Rat mesangial cells • Mice kidney tissues • Rat tubular epithelial cells |
• Expression is increased in DN and can enhance the production of high glucose-induced fibrotic and inflammatory markers | • DN [125] |
| miR-29* | • Human podocytes • Mouse mesangial cells • Mice kidney tissues • Mouse embryonic fibroblasts and tubular epithelial cells • Mice kidney glomeruli, endothelial cells, and podocytes |
• Low levels in early DN and fibrosis and can target collagens I and IV [116] • Lost with progressive renal fibrosis, can reduce collagens I and III, and interact with Smad3 [117] • miR-29c is increased in DN, induces cell apoptosis, and increases ECM protein accumulation [118] |
• DN [116,117,118] |
| miR-let-7b | • Rat proximal tubular epithelial cells • Mice kidney tissues |
• Is reduced in both diabetic and non-diabetic renal fibrosis and can regulate the expression of several ECM genes | • DN [114] |
| miR-93 | • Renal microvascular endothelial cells • Mouse podocytes • Mice kidney tissues |
• High glucose and diabetic conditions decrease miR-93 expressions • Can target VEGF and negatively regulate it |
• DN [115] |
| miR-200 * | • Human retinal endothelial cells • Mice and rat retinal tissues • Mice kidney tissues • Mouse mesangial cells • Mouse heart endothelial cells, vascular smooth muscle cells, and cardiac tissues |
• miR-200b is reduced under hyperglycemic and diabetic conditions [40,179]; can target VEGF [80,179] • Inhibition of miR-200a-3p can provoke renal fibrosis in DN [121] • Increased levels of miR-200b/c detected in diabetic mouse glomeruli; involved in glomerular mesangial hypertrophy [110,120] • miR-200b overexpression shown to prevent diabetes-induced changes in heart structure and function and reduce EndMT markers [134] • miR-200b shown to have a protective role in the diabetic retina [136,137] • Diabetic VSMCs exhibit increased miR-200 levels, which can contribute to inflammation [129] |
• DR [40,80,136,137] • DN [110,120,121,179] • DCM [129,134] |
| miR-146a | • Rat and mice retinal tissues • Human umbilical vein endothelial cells • Mice kidney tissues |
• miR-146a was shown to be reduced in diabetic tissues; miR-146a mimics can decrease FN expression [55] • miR-146a knockout exacerbates diabetes-induced inflammation and fibrosis in mice kidney tissues [126] • miR-146a mimics can prevent the increased expressions of ECM proteins and inflammatory markers in diabetic tissues [124] |
• DR [55] • DCM [55] • DN [124,126] |
| miR-1207-5b | • Human renal proximal tubule epithelial cells, podocytes, and mesangial cells | • Hyperglycemia shown to increase miR-1207-5b levels, which contributes to ECM accumulation in the kidney • Knockdown can decrease levels of TGF-β1, FN1, and PAI-1 |
• DN [122] |
| miR-302d | • Mice kidney tissues • Human mesangial cells, proximal tubular epithelial cells, and HEK-293T |
• Capable of attenuating TGF-β-induced fibronectin, thrombospondin, vimentin, and N-cadherin expressions • Can regulate TGF-β -induced EMT |
• DN [127] |
| miR-216a | • Primary mouse mesangial cells (MMCs) | • Upregulated by TGF-β in MMCs • Also increased in isolated renal glomeruli from type 1 and type 2 diabetic mice • Inhibiting miR-216a in MMCs reverses the effects of TGF-β on Pten and P-Akt levels |
• DN [145] |
| miR-217 | • Primary mouse mesangial cells | • Upregulated by TGF-β in MMCs • Also increased in diabetic mice kidneys • Along with miR-216a, miR-217 mimics can induce hypertrophy in MMCs |
• DN [145] |
| miR-133a | • Mice cardiac tissues • Neonatal rat myocytes |
• Downregulated in diabetic cardiomyopathy [131,132,133] • Mediates glucose-induced cardiomyocytes hypertrophy [131,132,133] • Cardiac-specific overexpression of miR-133a can significantly decrease cardiac fibrosis [133] |
• DCM [131,132,133] |
| miR-155 | • Mouse cardiac fibroblasts • Mouse bone marrow progenitor cells (BMPCs) |
• Increased expression of miR-155 in MI mice • Transplantation of BMPCs in MI mice can decrease miR-155 expressions and in association, show decreased cardiac fibrosis expressions |
• DCM [130] |
* indicates different reported effects of the miRNA in literature; DN = diabetic nephropathy; DR = diabetic retinopathy; DCM = diabetic cardiomyopathy; MI = myocardial infarction; ECM = extracellular matrix; VSMCs = vascular smooth muscle cells; VEGF = vascular endothelial growth factor; SIP1 = Smad-interacting protein 1; ZEB2 = Zinc Finger E-box Binding Homeobox 2; GFR = glomerular filtration rate; EMT = epithelial–mesenchymal transition; EndMT = endothelial–mesenchymal transition.