Kidney Week

Abstract: SA-PO257

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

Session Information

• Diabetic Kidney Disease: Basic - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 701 Diabetic Kidney Disease: Basic

Authors

• Peng, Fenfen, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China

Fenfen Peng, MD

• Zeng, Yao, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China

Yao Zeng, MD

• Ji, Yue, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China

Yue Ji, PhD

• Long, Haibo, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China

Haibo Long

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 P16^INK4A 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 P16^INK4A and renal injury marker NGAL, while circAkap7 overexpression decreased the SA-β-Gal activity and abolished the synthesis of P53, P21, and P16^INK4A 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.

Figure1. In vivo expression of circAkap7 ameliorates renal tubular senescence in db/db mice.

Figure2. CircAkap7 inhibits renal tubular epithelial cell senescence in vitro.

Funding

• Government Support – Non-U.S.