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.
Keywords: KLF4; chronic kidney disease; circPlekha7; miR-493-3p; renal fibrosis.
Chronic kidney disease (CKD) ultimately leads to complete kidney dysfunction. The incidence of CKD continues to rise as a result of the increasingly aging population, and the treatment is very limited. In this study, the authors identified a novel molecule, circPlekha7, that plays a crucial role in CKD development and progression. The level of circPlekha7 is lower in the kidney tissues of CKD patients, and increasing its level could attenuate kidney injury and fibrosis. This work helps researchers understand the disease better and, more importantly, provides new avenues to develop therapy.