miR-214 and Its Primary Transcript <i>Dnm3os</i> Regulate Fibrosis and Inflammation Through RAGE Signaling in Diabetic Kidney Disease
The mechanism of renoprotection as a result of receptor for advanced glycation end products (RAGE) deletion is unclear but seems to involve noncoding (ncRNAs). We investigated the regulation of ncRNAs by RAGE in the context of diabetic kidney disease (DKD), exploring the renal expression of ncRNAs, microRNAs, and fibrotic and inflammatory markers in diabetic RAGE-knockout (KO) and wild-type mice, as well as in mesangial cells (MCs) obtained ex vivo from these mice. Elevated miR-214 levels in diabetic RAGE-KO mice had antifibrotic effects by targeting protein diaphanous homolog 1 (DIAPH1). In contrast, the coexpressed host ncRNA, Dnm3os, had an opposite effect, enhancing fibrosis and inflammation in MCs. We propose a novel regulatory mechanism in DKD involving miR-214 and Dnm3os as negative and positive regulators of fibrosis, respectively, through the RAGE-DIAPH1 axis. Targeting DIAPH1 through miR-214 may represent a novel therapeutic strategy for DKD.
Authors
- Elif Ilhan Ekinci (ORCID: https://orcid.org/0000-0003-2372-395X)
- Mark Ziemann (ORCID: https://orcid.org/0000-0002-7688-6974)
- Tomohito Gohda (ORCID: https://orcid.org/0000-0002-0513-4433)
- Adrienne Laskowski
- Maki Murakoshi (ORCID: https://orcid.org/0000-0001-7920-269X)
- Phillip Kantharidis (ORCID: https://orcid.org/0000-0001-6260-1643)
- Melinda T. Coughlan (ORCID: https://orcid.org/0000-0001-8846-6443)
- Mark Emmanuel Cooper (ORCID: https://orcid.org/0000-0001-7785-2488)
- Brian G. Drew (ORCID: https://orcid.org/0000-0002-7839-9467)
- Jun Okabe (ORCID: https://orcid.org/0000-0002-7196-0522)
- Yusuke Suzuki (ORCID: https://orcid.org/0000-0002-4077-9747)
- Madhura Bose
- Shinji Hagiwara (ORCID: https://orcid.org/0000-0002-3125-4842)
- Aaron McClelland (ORCID: https://orcid.org/0000-0002-1957-7905)
- Karly C. Sourris
- Hiroko Sakuma (ORCID: https://orcid.org/0009-0006-0069-5553)
Institutions
- Baker Heart and Diabetes Institute (AU)
- The University of Melbourne (AU)
- Juntendo University (JP)
- Austin Health (AU)
- Tsurugi Hospital (JP)
- Monash University (AU)
Publication Details
- Journal
- Diabetes
- Published
- 2025-04-04
- DOI
- https://doi.org/10.2337/db24-0121
- Citations
- 4
- Primary Topic
- Advanced Glycation End Products research
- Type
- article
- Field-Weighted Citation Impact
- 5.27