Kidney Week

Abstract: TH-PO864

Irisin, a Myokine, Ameliorates Diabetic Nephropathy by Restoring Autophagy in Podocytes

Session Information

• Diabetic Kidney Disease: Basic - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Luo, Dan, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

Dan Luo,

• Zhao, Wenbo, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

Wenbo Zhao,

• Li, Yin, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

Yin Li,

• Lun, Yang Chieh, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

Yang Chieh Lun,

• Lin, Hongchun, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

Hongchun Lin,

• Lou, Tan-qi, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

Tan-qi Lou,

• Peng, Hui, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

Hui Peng,

Background

Moderate exercises have been demonstrated to ameliorate diabetic nephropathy in some clinical studies. However, the mechanism remains unknown. Skeletal muscle could excrete many myokines while exercises. Irisin is one of the myokines which could mediate the communication between muscle and other organs. Therefore, we hypothesis that exercised muscle-excreted irisin protects kidneys from diabetes mellitus.

Methods

We crossbred muscle-specific PGC-1α overexpression of mice (an animal model mimicking exercise) with db/m mice to get mPGC-1α-db/db mice. The urine albumin creatinine ratio (uACR) and pathologic change of kidneys were examined. Besides, recombinant irisin had been administrated to twelve-week-old db/db mice and their db/m littermates. The renal function and pathologic change were accessed to evaluate the protection effect of Irisin. Conditionally immortalized human podocyte cells were used for in vitro study to investigate how irisin protect podocytes from injury of high glucose (30mmol/l).

Results

There were significant accumulation of mesangial matrix, fusion of podocytes foot processes, widen of GBM as well as decrease of autophagy in the kidney of db/db mice. However, these kidney pathological injuries were remarkably improved in mPGC-1α-db/db mice. Meanwhile, the mice also showed significant alleviation of the excretion of uACR than db/db mice without mPGC-1α. These results indicate that mPGC-1α could alleviate kidney injury induced by diabetes. Irisin was found as one of the significantly increased myokines in the skeletal muscles of mPGC-1α mice, then we treated db/db mice with irisin for eight weeks. After peritoneal injection of irisin, the kidney pathologic change and microalbuminuria of db/db mice were all alleviated when compared to those db/db mice without irisin injection. Furthermore, Irisin treatment significantly restored autophagy in podocytes of db/db mice. Meanwhile, in vitro study, irisin improved the expression of autophagy related proteins and autophagy flux in high glucose cultured podocytes.

Conclusion

Our results indicate that the myokine, irisin, prevents the progression of diabetic nephropathy by restoring autophagy in podocytes. Irisin is one of the myokines that mediate the effect of exercised-muscle prevents diabetic nephropathy, which may become a new strategy to protect the kidney from diabetes.

Funding

• Government Support - Non-U.S.