Kidney Week

Abstract: SA-OR027

Klotho Ameliorates Diabetic Nephropathy via AMPK-PGC1α Mediated Renal Mitochondrial Protection

Session Information

• Diabetic Kidney Disease: Mechanisms, Models, and Modulators - II
  October 27, 2018 | Location: 5A, San Diego Convention Center
  Abstract Time: 05:42 PM - 05:54 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Lee, Jinho, Seoul National University Hospital, Seoul, Korea (the Republic of)

Jinho Lee



• Bodokhsuren, Tsogbadrakh Bodokhsuren, Seoul National University Hospital, Seoul, Korea (the Republic of)

Tsogbadrakh Bodokhsuren Bodokhsuren,

• Yun, Sohyun, Seoul National University Hospital, Seoul, Korea (the Republic of)

Sohyun Yun,

• Ryu, Hyunjin, Seoul National University Hospital, Seoul, Korea (the Republic of)

Hyunjin Ryu,

• Kang, Eunjeong, Seoul National University Hospital, Seoul, Korea (the Republic of)

Eunjeong Kang,

• Kang, Minjung, Seoul National University Hospital, Seoul, Korea (the Republic of)

Minjung Kang,

• Ahn, Curie, Seoul National University Hospital, Seoul, Korea (the Republic of)

Curie Ahn,

• Oh, Kook-Hwan, Seoul National University Hospital, Seoul, Korea (the Republic of)

Kook-Hwan Oh,

Background

Diabetic nephropathy(DN) is associated with renal mitochondrial injury, and decreased renal klotho. Klotho is known as ageing suppressor, and mitochondrial dysfunction is the hallmark of ageing. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a master regulator of mitochondrial biogenesis, and adenosine monophosphate-activated protein kinase(AMPK) is known as a guardian of mitochondria. Here, we report that recombinant klotho protein (rKL) is protective against DN in db/db mice by PGC1α-AMPK mediated mitochondrial recovery in the kidney.

Methods

We injected rKL into db/db and db/m mice for 8 weeks, and collected the serum and the kidney. Also, we treated rKL to various renal tubular cells in vitro, with or without 30mM high glucose (HG) exposed.

Results

rKL-treated db/db mice showed recovered renal proximal tubular mitochondria, as well as significantly reduced renal ROS and serum glucose, compared to vehicle-treated db/db mice. Also, rKL increased renal p-AMPK, PGC1α, and down-regulated mTOR/TGF-β in db/db mice. Moreover, we confirmed that rKL treatment ameliorated HG-mediated cellular damage, with an increase of PGC1α-AMPK induced mitochondrial recovery in cultured renal tubular cells.

Conclusion

Our data suggest a mitochondrial protective role of klotho against diabetic kidney disease by inducing AMPK-PGC1α expression.

a) renal mitochondiral recovery by rKL in db/db mice, and b) rKL increased renal p-AMPK and PGC1α expression in db/db mice.

Funding

• Government Support - Non-U.S.