Kidney Week

Abstract: FR-PO850

Effect of Klotho on Autophagy Clearance in Tacrolimus-Induced Renal Injury

Session Information

• Transplantation: Basic
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1801 Transplantation: Basic

Authors

• Lim, Sun Woo, The Catholic University of Korea, Seoul, Korea (the Republic of)

Sun Woo Lim,

• Shin, Yoo-Jin, College of Medicine, The Catholic University of Korea , Seoul, Korea (the Republic of)

Yoo-Jin Shin,

• Luo, Kang, The Catholic University of Korea, Seoul, Korea., Seoul, Korea (the Republic of)

Kang Luo,

• Quan, Yi, Seoul St. Mary''s Hospital, The Catholic University of Korea, Seoul, Korea (the Republic of)

Yi Quan,

• Ko, Eun jeong, Seoul St.Mary''s Hospital, Seoul, Korea (the Republic of)

Eun jeong Ko,

• Chung, Byung ha, Seoul St. Mary's Hospital , Seoul, Korea (the Republic of)

Byung ha Chung,

• Yang, Chul Woo, Seoul St. Mary's Hospital , Seoul, Korea (the Republic of)

Chul Woo Yang,

Group or Team Name

• Seoul St. Mary's Hospital, The Catholic University of Korea

Background

Recently, we showed that tacrolimus-induced renal injury is closely associated with impairment of autophagy clearance, and Klotho deficiency aggravates tacrolimus-induced renal injury. In this study, we evaluated the effect of Klotho treatment on autophagy clearance in tacrolimus-induced renal injury.

Methods

We evaluated the effect of Klotho on tacrolimus-induced renal injury in an experimental mouse model and in vitro by treatment with tacrolimus and/or recombinant mouse Klotho.

Results

In vivo and in vitro studies showed that tacrolimus treatment impaired lysosomal acidification and decreased cathepsin B activity, expression of lysosome-associated membrane protein 2, and transcription factor EB (TFEB), a master regulator for lysosomal biogenesis. These results were improved by Klotho treatment. Moreover, addition of bafilomycin A1, an inhibitor of lysosomal function, abolished the protective effect of Klotho, indicating that the protective effect of Klotho was closely associated with lysosome function. Klotho induced nuclear translocation of TFEB through inhibition of phosphorylation of glycogen synthase kinase 3β (GSK3β) by confirming using CHIR99021, a GSK3β inhibitor.

Conclusion

Collectively, our data suggest that Klotho improves autophagy clearance via activation of lysosomal function in tacrolimus-induced nephrotoxicity.