Key result
Type 2 diabetes mouse model reveals altered glomerular expression of 1,746 lncRNAs versus wild-type.
Why the study?
The molecular mechanisms underlying diabetic nephropathy in type 2 diabetes mellitus are largely unknown, and the role of long non-coding RNAs has been scarcely studied.
Hypothesis-generating for lncRNA roles in glomerular DN; leaves open relevance to human disease and therapeutic targeting.
The prevalence of type 2 diabetes mellitus (T2DM) and by association diabetic nephropathy (DN) will continuously increase in the next decades. Nevertheless, the underlying molecular mechanisms are largely unknown and studies on the role of new actors like long non-coding RNAs (lncRNAs) barely exist. In the present study, the inherently insulin-resistant mouse strain "black and tan, brachyuric" (BTBR) served as T2DM model. While wild-type mice do not exhibit pathological changes, leptin-deficient diabetic animals develop a severe T2DM accompanied by a DN, which closely resembles the human phenotype. We analyzed the glomerular expression of lncRNAs from wild-type and diabetic BTBR mice (four, eight, 16, and 24 weeks) applying the "GeneChip Mouse Whole Transcriptome 1.0 ST" array. This microarray covered more lncRNA gene loci than any other array before. Over the observed time, our data revealed differential expression patterns of 1746 lncRNAs, which markedly differed from mRNAs. We identified protein-coding and non-coding genes, that were not only co-located but also co-expressed, indicating a potentially cis-acting function of these lncRNAs. In vitro-experiments strongly suggested a cell-specific expression of these lncRNA-mRNA-pairs. Additionally, protein-coding genes, being associated with significantly regulated lncRNAs, were enriched in various biological processes and pathways, that were strongly linked to diabetes.
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Reichelt‐Wurm et al. (2019) studied Type 2 diabetes mellitus and diabetic nephropathy. Leptin deficiency (ob/ob mutation) / Type 2 diabetes vs. Wild-type BTBR mice was evaluated on Differential expression of glomerular lncRNAs (p=<0.05). In the BTBR mouse model of type 2 diabetes, 1,746 lncRNAs exhibited differential glomerular expression patterns over 24 weeks compared to wild-type mice.
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