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Abstract: FR-PO197

Honokiol Improves Diabetic Kidney Disease by Activating SIRT3 to Regulate Podocyte Mitochondrial Function

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Li, Ming, Nephrology department of The Third Affiated Hospital of Sun Yet-sen University, Guangzhou, China
  • Li, Canming, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, GUANGDONG, China
  • Ye, Zengchun, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, GUANGDONG, China
  • Peng, Hui, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, GUANGDONG, China
  • Lou, Tan-qi, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, GUANGDONG, China
Background

Diabetic kidney disease(DKD) is the main cause of end-stage renal disease. Current studies have shown that podocyte mitochondrial dysfunction is closely related to the progression of DKD.

Methods

Eight-week-old db/db and db/m mice were injected with honokiol(HKL,5 mg/kg)intraperitoneally for 5 consecutive days.STZ was used to induce diabetes mellitus models in wild type(WT) and SIRT3 knockout (SIRT3 KO) mice and HKL was injected intraperitoneally for 5 days.ACR of mice in each group were detected.The morphological changes of mitochondria were observed under electron microscopes. The activity of podocytes mitochondrial complex I and II were detected by extracting mitochondrial DNA. The expression of mitochondrial metabolism related genes and mitochondrial DNA copys was detected by RT-PCR.In vitro,western blot was used to detect the expression of SIRT3 in podocytes after high glucose stimulation for 48h with or without HKL(5umol/L). Mitotraker, Mitosox and TMRM kits were used to detect the morphology and function of mitochondria. Flow cytometry (V-FITC/PI) was used to detect the apoptosis of podocytes.

Results

The expression of mitochondrial complex I and II in podocytes of db/db mice was lower than that of db/m mice, accompanied by the decrease of mitochondrial DNA Copys.The expressions of SIRT3, PGC1α and TFAM in db/db mice were significantly lower compared with db/m mice.The number of podocytes in db/db mice was decreased by immunohistochemistry.It was found that HKL restore the expression of SIRT3 in podocytes of db/db mice and STZ-induced diabetic mice.Aslo,the mice treated with HKL had lower ACR and improved mitochondrial morphology, but no significant improvement in SIRT3 KO mice. The expression of mitochondrial complex I, II, mitochondrial DNA Copys in podocytes of db/db mice and WT mice were upregulated by HKL. In vitro ,it was also found that HKL could upregulate the expression of SIRT3 in podocytes. Compared with high glucose alone, mitochondrial membrane potential decreased in podocytes co-stimulated by high glucose and HKL, and ROS production decreased.Also,flow cytometry (V-FITC/PI) showed that podocyte apoptosis was reduced with HKL incubation.

Conclusion

Honokiol can improve the morphology and function of podocyte mitochondria by upregulating the expression of SIRT3, thus reduce the apoptosis of podocytes.

Funding

  • Government Support - Non-U.S.