| First Author | Guo J | Year | 2023 |
| Journal | Cell Death Dis | Volume | 14 |
| Issue | 2 | Pages | 172 |
| PubMed ID | 36854759 | Mgi Jnum | J:345332 |
| Mgi Id | MGI:7440395 | Doi | 10.1038/s41419-023-05695-2 |
| Citation | Guo J, et al. (2023) Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3beta signaling pathway. Cell Death Dis 14(2):172 |
| abstractText | Progressive albuminuria is the primary clinical symptom of diabetic nephropathy (DN), leading to a gradual decline in kidney function. DLX6-AS1 was the first reported long non-coding RNA (lncRNA) to participate in organogenesis and play crucial roles in the brain or neural cell development. Herein, we investigated the DLX6-AS1 (Dlx6-os1 in mice) role in DN pathogenesis. We found that DLX6-AS1 expression in DN patients correlated with the extent of albuminuria. Dlx6-os1 overexpression induced cellular damage and inflammatory responses in cultured podocytes through miR-346-mediated regulation of the GSK-3beta pathway. In various established diabetic and newly developed knockout mouse models, Dlx6-os1 knockdown/knockout significantly reduced podocyte injury and albuminuria. The Dlx6-os1 effects were remarkably modulated by miR-346 mimics or mutants and significantly diminished in podocyte-specific GSK-3beta-knockout mice. Thus, DLX6-AS1 (Dlx6-os1) promotes DN development by accelerating podocyte injury and inflammation through the upregulation of the GSK-3beta pathway, providing a novel molecular target for DN therapy. |
