The LncRNA6524/miR-92a-2-5p/Dvl1/Wnt/β-catenin axis promotes renal fibrosis in the UUO mouse model
LncRNAs are reported to participate in multiple biological and pathological processes, including renal fibrosis due to obstructive nephropathy. However, the function and mechanisms of each lncRNA in this context differ. In this study, we created a fibrosis model in vitro using TGF-β1 treatment and i...
Gespeichert in:
Veröffentlicht in: | Archives of biochemistry and biophysics 2024-11, Vol.761, p.110175, Article 110175 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | LncRNAs are reported to participate in multiple biological and pathological processes, including renal fibrosis due to obstructive nephropathy. However, the function and mechanisms of each lncRNA in this context differ. In this study, we created a fibrosis model in vitro using TGF-β1 treatment and in vivo through unilateral ureteral obstruction. We demonstrated that lncRNA6524 expression increased in both models, as confirmed by qPCR. Additionally, we discovered that lncRNA6524 mediates the TGF-β1-induced accumulation of extracellular matrix (ECM) proteins in BUMPT cells. We investigated the mechanism using dual luciferase reporter assays, immunofluorescence, and qPCR. Our results indicate that lncRNA6524 acts as a sponge for miR-92a-2-5p, promoting renal fibrosis by upregulating the Dvl1/Wnt/β-catenin signaling pathway. In summary, our findings demonstrate a linear regulatory relationship among lncRNA6524, miR-92a-2-5p, and the Dvl1/Wnt/β-catenin axis in renal epithelial cells during kidney obstruction. This highlights a new potential target for treating obstruction-related renal fibrosis.
Unilateral Ureteral Obstruction (UUO) and Transforming Growth Factor Beta (TGFβ) increase the expression of LncRNA6524 in proximal tubular epithelial cells. LncRNA6524 acts as a sponge for miR-92a-2-5p. This microRNA targets Dvl1, leading to a decrease in its protein level. Dvl1 exerts a pro-fibrotic role by stabilizing β-catenin. LncRNA6524 promotes renal fibrosis induced by UUO and TGFβ by regulating the miR-92a-2-5p/Dvl1/Wnt/β-catenin signaling axis. [Display omitted]
•The expression of LncRNA6524 was increased in mice underwent unilateral ureteral obstruction.•LncRNA6524 exerts a pro-fibrotic role in the UUO model through sponging miR-92a-2-5p.•MiR-92a-2-5p targets Dvl1, which regulates Wnt/β-catenin signaling pathway to promote renal fibrosis. |
---|---|
ISSN: | 0003-9861 1096-0384 1096-0384 |
DOI: | 10.1016/j.abb.2024.110175 |