Long Noncoding RNAs in Diabetic Nephropathy

Diabetic nephropathy represents a leading cause of end-stage renal disease worldwide, characterised by glomerular hypertrophy, extracellular matrix accumulation and progressive loss of renal function. In recent years, long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression in this setting, acting through epigenetic, transcriptional and post-transcriptional mechanisms. These transcripts modulate key pathogenic processes including podocyte injury, mesangial cell proliferation, inflammatory signalling and epithelial–mesenchymal transition. By interacting with RNA-binding proteins, miRNA networks and chromatin modifiers, lncRNAs influence cytokine production, matrix remodelling and cell survival under hyperglycaemic stress. Preclinical studies have demonstrated that dysregulation of specific lncRNAs correlates with glomerulosclerosis, tubulointerstitial fibrosis and proteinuria, highlighting their potential utility as biomarkers. Moreover, targeted manipulation of lncRNA expression in animal models attenuates renal fibrosis and inflammation, offering promising avenues for novel diagnostic and therapeutic strategies in diabetic kidney disease.

Research from Nature Portfolio

Recent foundational work has revealed a complex lncRNA-hosted microRNA megacluster that drives early features of diabetic nephropathy. In murine models, an endoplasmic reticulum stress-regulated lncRNA transcript (lnc-MGC) coordinately elevates nearly forty embedded microRNAs in glomeruli exposed to high glucose or TGF-β1. This cluster promotes extracellular matrix accumulation and glomerular hypertrophy via suppression of protein synthesis regulators and enhancement of ER stress pathways. Genetic deletion of the stress-responsive transcription factor CHOP reduces both lnc-MGC and its microRNA suite, conferring renal protection. Antisense oligonucleotide targeting of lnc-MGC in diabetic mice diminishes cluster microRNA expression, alleviates mesangial expansion and limits fibrotic responses, demonstrating translational potential for early intervention.

Long Noncoding RNAs in Diabetic Nephropathy publication trend

The graph below shows the total number of articles in long noncoding rnas in diabetic nephropathy across all publications each year (not limited to Nature Index journals).

Technical terms

Long noncoding RNA (lncRNA): RNA transcript longer than 200 nucleotides that does not code for protein but regulates gene expression at multiple levels.

Podocyte: specialised epithelial cell in the glomerulus essential for maintaining the filtration barrier and preventing proteinuria.

Mesangial cell: intraglomerular cell that provides structural support, regulates capillary blood flow and contributes to matrix production.

Epithelial–mesenchymal transition (EMT): cellular programme in which epithelial cells acquire mesenchymal characteristics, promoting fibrosis and tissue remodelling.

Extracellular matrix (ECM): network of proteins and polysaccharides secreted by cells that provides structural scaffold and influences cell behaviour.

References

1. Long noncoding RNA ENST00000436340 promotes podocyte injury in diabetic kidney disease by facilitating the association of PTBP1 with RAB3B. Cell Death & Disease (2023).
2. LncRNA KIFAP3-5:1 inhibits epithelial-mesenchymal transition of renal tubular cell through PRRX1 in diabetic nephropathy. Cell Biology and Toxicology (2024).
3. LncRNA H19: a novel player in the regulation of diabetic kidney disease. Frontiers in Endocrinology (2023).
4. An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy. Nature Communications (2016).