Kidney Week

Abstract: SA-PO314

Klotho Ameliorates Diabetic Glomerulonephritis by Suppressing TRPC6 in Podocytes

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

• 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

Glomerular podocyte injury is the hallmark of diabetic nephropathy (DN). This damage is related with increase of transient receptor potential channel 6 (TRPC6) calcium channel in podocytes, mediating calcium influx, thus causing foot process effacement. Since klotho is reported as a TRPC6-suppressing factor in nephrectomized mice, we hypothesized that klotho may also inhibit diabetes-induced TRPC6 up-regulation in podocytes, thereby reduce albuminuria.

Methods

We injected recombinant klotho protein (rKL) into db/db and db/m mice for 8 weeks, and collected the urine and the kidney. We treated rKL to cultured podocytes, with or without high glucose (HG, 30mM) exposed.

Results

rKL treated db/db mice showed dramatic glomerular recovery, including amelioration of basement membrane thickening and foot process effacement, as well as remarkably reduced albuminuria. We also confirmed increased renal expression of TRPC6 and its downstream molecules, PI3K and calcineurin in diabetic mice, were normalized by rKL. Next, we analyzed TRPC6, PI3K and calcineurin in podocytes. HG-mediated increase of TRPC6 in podocytes is normalized by rKL treatment, showing improved cell survival and reduced intracellular calcium in HG environment.

Conclusion

Our data reveals that klotho protects the podocytes in diabetic condition by suppression of TRPC6.

rKL treat to db/db mice induced: a) reduced albuminuria, and b) glomerular recovery.