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circPlekha7 suppresses renal fibrosis via targeting miR-493-3p/KLF4
Wa Zhou1, Yan-Xia Chen1, Ben Ke1
1Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, PR China.
Abstract:
Aims: The authors aim to investigate the function of circPlekha7 in renal fibrosis. Methods: Human renal tissues from chronic kidney disease patients, kidney cell line and primary cultured renal tubular epithelial cells were used. TGF-β1-treated human kidney 2 cells/tubular epithelial cells and a unilateral ureteral obstruction mouse model were employed to study renal fibrosis. Results: circPlekha7 was diminished in renal tissues from chronic kidney disease patients and TGF-β1-treated human kidney 2 cells and tubular epithelial cells, while miR-493-3p was upregulated. Overexpression of circPlekha7 or knockdown of miR-493-3p suppressed TGF-β1 induced enhancements on epithelial to mesenchymal transition and fibrogenesis, as well as attenuated renal fibrosis and injury in mice subjected to unilateral ureteral obstruction. circPlekha7 bound with miR-493-3p, which directly targeted KLF4. Conclusion: circPlekha7 inhibits epithelial to mesenchymal transition of renal tubular epithelial cells and fibrosis via targeting miR-493-3p to de-repress KLF4/mitofusin2 expression.
Insights
Circular RNA circPlekha7 inhibits kidney fibrosis by targeting miR-493-3p, thereby de-repressing KLF4/mitofusin2 expression. This finding offers a potential therapeutic target for chronic kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Renal fibrosis is a common pathological process in chronic kidney disease (CKD).
- Epithelial-to-mesenchymal transition (EMT) plays a crucial role in the development of renal fibrosis.
- The function of circular RNAs (circRNAs) in renal fibrosis remains largely unknown.
Purpose of the Study:
- To investigate the role and mechanism of circPlekha7 in renal fibrosis.
- To explore the potential of circPlekha7 as a therapeutic target for CKD.
Main Methods:
- Analysis of circPlekha7 and miR-493-3p expression in human CKD renal tissues and cell models.
- In vitro studies using TGF-β1-treated kidney cells to induce EMT and fibrosis.
- In vivo studies using a unilateral ureteral obstruction (UUO) mouse model to mimic renal fibrosis.
Main Results:
- circPlekha7 expression was significantly decreased in CKD tissues and TGF-β1-treated cells, while miR-493-3p was upregulated.
- Overexpression of circPlekha7 or inhibition of miR-493-3p suppressed TGF-β1-induced EMT and fibrogenesis.
- circPlekha7 directly interacted with miR-493-3p, and miR-493-3p targeted KLF4.
- circPlekha7 overexpression attenuated renal fibrosis and injury in the UUO mouse model.
Conclusions:
- circPlekha7 acts as a tumor suppressor in renal fibrosis by inhibiting EMT.
- The circPlekha7/miR-493-3p/KLF4 axis is a key regulatory pathway in renal fibrosis.
- circPlekha7 may serve as a novel therapeutic biomarker for CKD.
