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Kidney Week

Abstract: FR-PO977

Metformin Ameliorates Kidney Injury of Tsc1ptKO Mice Through AMPK/AKT Pathway

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • Fang, Yili, Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China
  • Zhang, Zhigang, Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China
  • Wu, Huijuan, Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China
Background

As an intractable branch among chronic kidney diseases, tuberous sclerosis complex (TSC) in kidney usually expresses kidney enlargement, increasing cysts, interstitial fibrosis and serious damage on renal function. One of the critical mechanism underlies TSC is aberrant down-regulation of 5’AMP-activated protein kinase (AMPK) phosphorylation. Indicated by several researches, metformin showed excellent functions in reducing inflammation and inhibiting proliferation through AMPK phosphorylation, as well as decreasing the level of interstitial fibrosis. Therefore, we investigated whether metformin could induce the amelioration of kidney injury in TSC.

Methods

Firstly, we established the Tsc1 knockout in proximal tubule (Tsc1ptKO) mice model, which caused striking kidney growth. Then we performed metformin by intraperitoneal injection in Tsc1ptKO mice by 1 week of age for 1-3 weeks every day.

Results

We observed that metformin significantly reduced kidney growth in Tsc1ptKO mice by 4 weeks of age, with obvious shrunken kidneys size, decreased amount and size in cysts as well as obvious decline in proteinuria and serum creatinine level. Besides, immunochemistry showed metformin inhibited proliferation and induced apoptosis of proximal tubular epithelial cells in Tsc1ptKO mice, meanwhile reduced inflammation and interstitial fibrosis. The above alterations were induced by apparent AMPK phosphorylation under the influence of metformin, which was confirmed by immunoblotting and immunochemistry.

Conclusion

Altogether, these results proved the amelioration effect of metformin on the kidney injury of Tsc1ptKO, which provides an innovative idea for clinical treatment on TSC and related kidney diseases.