Kidney Week

Abstract: SA-PO308

Protecting Glomerular Disease Progression in Mice Lacking Podocyte Associated Talin1 by Tangshen Formula

Session Information

• Cellular Crosstalk in Glomerular Diseases - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

• Zhao, Tingting, China-Japan Friendship Hospital, Beijing, China

Tingting Zhao,

• Tian, Xuefei, Yale University, New Haven, Connecticut, United States

Xuefei Tian,

• Li, Ping, China-Japan Friendship Hospital, Beijing, China

Ping Li,

• Ishibe, Shuta, Yale University School of Medicine, New Haven, Connecticut, United States

Shuta Ishibe,

Background

Loss of podocyte associated talin1 in mice results in severe proteinuria and kidney failure. Tangshen Formula (TSF), a traditional Chinese Medicine, has been confirmed to play a renal protective effect in rats with diabetic kidney disease and in patients with type 2 diabetic kidney disease. In this study, we further investigate the effect of TSF in genetic mouse model of disease where robust proteinuria is evident.

Methods

Twelve 8 weeks old Tln1^fl/fl Pod-rtTA TetO-Cre mice (iTln1 KO) were induced with doxycycline for three weeks to specifically delete talin1 expression in the podocytes. After 2 weeks of doxycycline induction, the mice were separated into two groups +/- TSF treatment (6 vs 6). TSF were delivered by oral gavage at a dosage of 2.4g/Kg body weight/day for total of 5 weeks.

Results

Two weeks of doxycycline induction in the iTln1 KO mice, resulted in robust albuminuria prior to treatment (TSF treatment group: 817.35 ± 69.99 vs 53.02 ±10.34 µg/mg creatinine; Placebo treatment group: 781.97 ±72.70 vs 63.49 ±15.52 µg/mg creatinine) measured by ELISA. Following TSF or Placebo treatment for 5 weeks, TSF treatment in the iTln1 KO mice significantly reduced albuminuria compared to the placebo group (2136.88 ±270.32 vs 4028.4±516.67 µg/mg creatinine, P<0.05). TSF treatment in the iTln1 KO mice improved renal function measured by plasma creatinine (0.46±004 mg/dl to 0.33±0.03 mg/dl. P<0.05). TSF treatment in iTln1 KO mice ameliorated glomerulosclerosis and inhibited tubulointerstitial injury including interstitial fibrosis, tubular dilatation, and proteinaceous casts. Ultrastructural examination by transmission electron micrographs also showed improvement in foot process effacement and thickness of the basement membrane in iTln1 KO mice treated with TSF.

Conclusion

These results suggest a potential therapeutic role of TSF mice with proteinuric kidney disease and may have a protective role in human glomerulonephropathies.

Funding

• Government Support - Non-U.S.