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Updated: Sep 9, 2025

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Published on: May 2, 2025
Cell Type-Specific Expression of Long Noncoding RNAs in Human Diabetic Kidneys Identifies TARID as a Key Regulator of
Juliette A de Klerk1,2, Roderick C Slieker2, Wilson C Parker3
1Division of Nephrology and the Einthoven Laboratory for Vascular and Regenerative Medicine. Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
This study identifies kidney-specific long noncoding RNAs (lncRNAs) and reveals their role in kidney health. A specific lncRNA, TARID, is upregulated in diabetic kidney disease and affects podocyte function.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics
Background:
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cellular processes.
- Understanding cell type-specific lncRNA expression is crucial for deciphering kidney function and disease.
- Dysregulation of gene expression is a hallmark of diabetic kidney disease (DKD).
Purpose of the Study:
- To create a comprehensive resource of cell type-specific lncRNA expression in the human kidney.
- To investigate the role of lncRNAs in maintaining renal health.
- To identify lncRNAs dysregulated in diabetic kidney disease.
Main Methods:
- Single-cell RNA sequencing and bioinformatics analyses were employed to identify and profile lncRNAs.
- Comparative analysis of lncRNA expression in healthy versus diabetic kidney tissue.
- Functional studies using cell culture models to assess the impact of specific lncRNAs on podocyte biology.
Main Results:
- A catalog of 174 cell type-specific lncRNAs in the human kidney was established.
- 54 lncRNAs exhibited altered expression patterns in diabetic kidney disease.
- TCF21 antisense RNA inducing promoter demethylation (TARID), a podocyte-specific lncRNA, was found to be upregulated in DKD and essential for podocyte actin cytoskeleton organization.
Conclusions:
- Cell type-specific lncRNAs are integral to human kidney physiology and pathophysiology.
- TARID is a key lncRNA in podocytes, implicated in the pathogenesis of diabetic kidney disease.
- This study provides a valuable resource for future research into lncRNA-mediated mechanisms in kidney health and disease.
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