MicroRNA in diabetic nephropathy
Identifying molecular pathways associated with diabetic nephropathy is a high priority in the field. We have recently examined the role of microRNAs (miRs) in renal injury. miRs are small noncoding RNAs that regulate gene expression, and their dysregulation has been implicated in a number of disease processes. To determine if miRs play a critical role in the regulation of responses to renal injury, we performed global miR expression profiling on RNA isolated from kidneys following warm or cold ischemia followed by reperfusion. Analysis of miR expression in kidneys of mice that underwent warm ischemia reperfusion injury (IRI) revealed 9 miRs that are differentially expressed in a lymphocyte independent manner when compared with controls. 7/9 of these miRs were also differentially expressed in kidneys that underwent cold IRI, indicating a common molecular signature of kidney damage following IRI. Mathematical analysis indicate that differentially regulated miR expression comprise a molecular fingerprint of renal injury resulting from IRI. The goal of this proposal is to determine if miR expression profiling can similarly be used to identify a molecular fingerprint of diabetic nephropathy. This pilot study seeks to explore the use of differential expression of miRs as a novel assay that may eventually be useful for diagnosing and pronosing diabetic nephropathy, as well as to uncover novel pathways that contribute to diabetic nephropathy. The specific aims of this proposal are: 1, Test the hypothesis that differential expression of miRs can be used as a biomarker of diabetic nephropathy; and 2, identify potential targets of differentially expressed miRs in diabetic nephropathy. All miRs have the potential to regulate gene expression, therefore, understanding how their expression is altered through progression of diabetic nephropathy uniquely lends itself to the development of phenotyping assays or biomarkers of renal injury resulting from diabetic nephropathy, as well as the identification of novel targets of regulation that may lead to the discovery of new pathways involved in disease progression. This proposal therefore represents a new area of investigation that could profoundly change how diabetic nephropathy is diagnosed and treated.

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