CircAkap7 Downregulation Promotes Renal Tubular Epithelial Cell Senescence in Diabetic Kidney Disease

Background: Diabetic kidney disease (DKD) exhibits an accelerated tubular epithelial cell senescent phenotype. Our previous studies showed that downregulation of circAkap7 promotes renal fibrosis in DKD. Methods: Ultrasound mediated gene transfer of circAkap7 plasmids into the kidneys of db/db mice is used. Mouse primary renal tubular epithelial cells (mPTECs) was isolated and cultured in DMEM/F12 medium. Results: As shown in Figure 1, the SA-β-gal activity and senescence markers P53, P21, and P16INK4A were significantly decreased in the db/db mice with circAkap7 overexpression. Two SASP factors, TGF-β1 and IL-6 were found to be decreased in db/db mice with circAkap7 overexpression. As shown in Figure 2, the mPTECs transfected with circAkap7 siRNA showed an increase in G1-phase cells and a decrease in S-phage cells . Knockdown of circAkap7 increased the level of SA-β-gal staining, P53, P21 and P16INK4A andrenal injury marker NGAL, while circAkap7 overexpression decreased the SA-β-Gal activity and abolished the synthesis of P53, P21, and P16INK4A induced by the high-glucose. Medium derived from mPTECs transfected with si-circAkap7 can promotes the synthesis of fibronectin and α-SMA in fibroblast. Conclusion: Downregulation of circAkap7 promotes renal tubular senescence in DKD. Funding: Government Support – Non-U.S.Figure1. In vivo expression of circAkap7 ameliorates renal tubular senescence in db/db mice.Figure2. CircAkap7 inhibits renal tubular epithelial cell senescence in vitro.