Figure 8.

DN stage–specific regulation of miRNAs: humans (~ late stage) versus animal models (~ early stage). Usually, renal biopsies are obtained from diabetic patients at the middle or late stage of DN because they present with micro- or macro-albuminuria, glomerular filtration rate (GFR) decline, or other clear symptoms of renal dysfunction. When compared, most RNAs (including coding and noncoding) are likely to depict lower expression in the end stage of DN relative to the intermediate stage. It might be interpreted that downregulation of RNA is associated with renal failure; however, decreases in RNA expression could be due to poor quality of RNAs in end-stage biopsies. In experimental models of DN, animals can be systematically monitored from the healthy to more advanced stages of renal disease, although most mouse models used to study miRNAs do not depict features of human DN. Therefore, some miRNAs found to be upregulated in the early stage of DN in animal experiments may appear to be downregulated in samples from humans who are in much later stages of DN, due to poor sample quality or non-comparable stages. Thus, miRNAs that are induced in early DN in animal models can be potentially assessed as therapeutic targets in humans because their inhibition might slow down progression to late- or end-stage disease even before clear symptoms are evident.