The 24 h urine albumin excretion rate of diabetic db/db mice decreased after exposure to elevated miR-21. The same study also identified PTEN as a target of miR-21.38 Another study has reported overexpression of miR-377 in human and mouse mesangial cells when exposed to high glucose levels.39 MiR-377 has been demonstrated to reduce the expression of p21-activated kinase (PAK1) and manganese superoxide dismutase (mnSOD). This enhances fibronectin production, which is characteristic of mesangial cells in diabetic nephropathy. We anticipate that many other miRNAs learn more expressed in podocytes, tubular and other renal cells will be deregulated under hyperglycaemic conditions. In diabetic nephropathy,
alteration of miRNA expression in response to several pathophysiological states is of interest, notably hypoxic-ischaemic and hyperglycaemic stimuli. The findings by Wang and colleagues have already provided the first glimpse of the effects of hyperglycaemia on miRNA expression in mesangial cells. In addition, hyperglycaemia has been found to affect endothelial dysfunction through miR-221.40 Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited renal diseases. Genetically, mutations in the polycystic kidney disease-1 gene (PKD1) account for 85%
of ADPKD; whereas mutations in the polycystic kidney disease-2 gene (PKD2) are responsible for the remainder.41 PKD2 encodes a protein termed polycystin-2. Aberrant expression of polycystin-2 causes abnormal proliferation of renal tubular and biliary epithelial cells, eventually leading to cystogenesis.42,43 check details The potential role of microRNAs in control of expression of PKD genes and in mediating functional effects has recently been explored. Two groups have demonstrated
that miR-17 directly targets the 3′UTR of PKD2 and post-transcriptionally represses the expression of PKD2.44,45 Moreover, they also showed that overexpression of miR-17 may promote cell proliferation via post-transcriptional repression of PKD2 in HEK293T cells. Finding new miRNAs that target PKD1 is an area of active research. Using a rat model of PKD, 30 differentially Inositol oxygenase expressed miRNAs have been identified in diseased kidney tissues compared with healthy rat, 29 of which are downregulated.46 Two algorithms: TargetScan and miRanda, predicted targets for significantly deregulated miRNAs in PKD that were correlated with pathways affected in PKD as determined using KEGG, GeneOntology (GO), Biocarta and the Molecular Signature databases.47–50 The deregulated miRNAs in PKD were associated with genes in 24 functional categories, including several pathways important to cyst formation such as mTOR signalling, mitogen-activated protein kinase signalling, Wnt signalling and TGF-β pathway.46 However, these correlations require experimental validation. MiR-15a has been reported to modulate the expression of cell cycle regulator Cdc25A and affect hepatic cystogenesis in a rat model of PKD.